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Immune Response-Mediated Protection of Adult but Not Neonatal Mice from Neuron-Restricted Measles Virus Infection and Central Nervous System Disease

Lawrence, Diane M. P.; Vaughn, Melinda M.; Belman, Alec R.; Cole, Joan S.; Rall, Glenn F.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/1999 EN
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In many cases of neurological disease associated with viral infection, such as measles virus (MV)-induced subacute sclerosing panencephalitis in children, it is unclear whether the virus or the antiviral immune response within the brain is the cause of disease. MV inoculation of transgenic mice expressing the human MV receptor, CD46, exclusively in neurons resulted in neuronal infection and fatal encephalitis within 2 weeks in neonates, while mice older than 3 weeks of age were resistant to both infection and disease. At all ages, T lymphocytes infiltrated the brain in response to inoculation. To determine the role of lymphocytes in disease progression, CD46+ mice were back-crossed to T- and B-cell-deficient RAG-2 knockout mice. The lymphocyte deficiency did not affect the outcome of disease in neonates, but adult CD46+ RAG-2− mice were much more susceptible to both neuronal infection and central nervous system disease than their immunocompetent littermates. These results indicate that CD46-dependent MV infection of neurons, rather than the antiviral immune response in the brain, produces neurological disease in this model system and that immunocompetent adult mice, but not immunologically compromised or immature mice, are protected from infection.

Respiratory Syncytial Virus Infection and G and/or SH Protein Expression Contribute to Substance P, Which Mediates Inflammation and Enhanced Pulmonary Disease in BALB/c Mice

Tripp, Ralph A.; Moore, Deborah; Winter, Jorn; Anderson, Larry J.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2000 EN
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66.971963%
A distinct clinical presentation of respiratory syncytial virus (RSV) infection of humans is bronchiolitis, which has clinical features similar to those of asthma. Substance P (SP), a tachykinin neuropeptide, has been associated with neurogenic inflammation and asthma; therefore, we chose to examine SP-induced inflammation with RSV infection. In this study, we examined the production of pulmonary SP associated with RSV infection of BALB/c mice and the effect of anti-SP F(ab)2 antibodies on the pulmonary inflammatory response. The peak production of pulmonary SP occurred between days 3 and 5 following primary RSV infection and day 1 after secondary infection. Treatment of RSV-infected mice with anti-SP F(ab)2 antibodies suggested that SP may alter the natural killer cell response to primary and secondary infection. In mice challenged after formalin-inactivated RSV vaccination, SP appears to markedly enhance pulmonary eosinophilia as well as increase polymorphonuclear cell trafficking to the lung. Based on studies with a strain of RSV that lacks the G and SH genes, the SP response to RSV infection appears to be associated with G and/or SH protein expression. These data suggest that SP may be an important contributor to the inflammatory response to RSV infection and that anti-SP F(ab)2 antibodies might be used to ameliorate RSV-associated disease.

Tissue Sites of Persistent Infection and Active Replication of Equine Infectious Anemia Virus during Acute Disease and Asymptomatic Infection in Experimentally Infected Equids

Harrold, Sharon M.; Cook, Sheila J.; Cook, R. Frank; Rushlow, Keith E.; Issel, Charles J.; Montelaro, Ronald C.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /04/2000 EN
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Equine infectious anemia virus (EIAV) infection of horses is characterized by recurring cycles of disease and viremia that typically progress to an inapparent infection in which clinical symptoms are absent as host immune responses maintain control of virus replication indefinitely. The dynamics of EIAV viremia and its association with disease cycles have been well characterized, but there has been to date no comprehensive quantitative analyses of the specific tissue sites of EIAV infection and replication in experimentally infected equids during acute disease episodes and during asymptomatic infections in long-term inapparent carriers. To characterize the in vivo site(s) of viral infection and replication, we developed a quantitative competitive PCR assay capable of detecting 10 copies of viral DNA and a quantitative competitive reverse transcription-PCR assay with a sensitivity of about 30 copies of viral singly spliced mRNA. Animals were experimentally infected with one of two reference viruses: the animal-passaged field isolate designated EIAVWyo and the virulent cell-adapted strain designated EIAVPV. Tissues and blood cells were isolated during the initial acute disease or from asymptomatic animals and analyzed for viral DNA and RNA levels by the respective quantitative assays. The results of these experiments demonstrated that the appearance of clinical symptoms in experimentally infected equids coincided with rapid widespread seeding of viral infection and replication in a variety of tissues. During acute disease...

Noninvasive Bioluminescence Imaging of Herpes Simplex Virus Type 1 Infection and Therapy in Living Mice

Luker, Gary D.; Bardill, J. Patrick; Prior, Julie L.; Pica, Christina M.; Piwnica-Worms, David; Leib, David A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /12/2002 EN
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Mouse models of herpes simplex virus type 1 (HSV-1) infection provide significant insights into viral and host genes that regulate disease pathogenesis, but conventional methods to determine the full extent of viral spread and replication typically require the sacrifice of infected animals. To develop a noninvasive method for detecting HSV-1 in living mice, we used a strain KOS HSV-1 recombinant that expresses firefly (Photinus pyralis) and Renilla (Renilla reniformis) luciferase reporter proteins and monitored infection with a cooled charge-coupled device camera. Viral infection in mouse footpads, peritoneal cavity, brain, and eyes could be detected by bioluminescence imaging of firefly luciferase. The activity of Renilla luciferase could be imaged after direct administration of substrate to infected eyes but not following the systemic delivery of substrate. The magnitude of bioluminescence from firefly luciferase measured in vivo correlated directly with input titers of recombinant virus used for infection. Treatment of infected mice with valacyclovir, a potent inhibitor of HSV-1 replication, produced dose-dependent decreases in firefly luciferase activity that correlated with changes in viral titers. These data demonstrate that bioluminescence imaging can be used for noninvasive...

Susceptibility of Immature and Mature Langerhans Cell-Type Dendritic Cells to Infection and Immunomodulation by Human Cytomegalovirus

Hertel, Laura; Lacaille, Vashti G.; Strobl, Herbert; Mellins, Elizabeth D.; Mocarski, Edward S.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /07/2003 EN
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Human cytomegalovirus (CMV) infection initiates in mucosal epithelia and disseminates via leukocytes throughout the body. Langerhans cells (LCs), the immature dendritic cells (DCs) that reside in epithelial tissues, are among the first cells to encounter virus and may play important roles in the immune response, as well as in pathogenesis as hosts for viral replication and as vehicles for dissemination. Here, we demonstrate that CD34+ progenitor cell-derived LC-type DCs exhibit a differentiation state-dependent susceptibility to CMV infection. In contrast to the small percentage (3 to 4%) of the immature LCs that supported infection, a high percentage (48 to 74%) of mature, LC-derived DCs were susceptible to infection with endotheliotropic strains (TB40/E or VHL/E) of CMV. These cells were much less susceptible to viral strains AD169varATCC, TownevarRIT3, and Toledo. When exposed to endotheliotropic strains, viral gene expression (IE1/IE2 and other viral gene products) and viral replication proceeded efficiently in LC-derived mature DCs (mDCs). Productive infection was associated with downmodulation of cell surface CD83, CD1a, CD80, CD86, ICAM-1, major histocompatibility complex (MHC) class I, and MHC class II on these cells. In addition...

Influence of Maternal Filariasis on Childhood Infection and Immunity to Wuchereria bancrofti in Kenya

Malhotra, Indu; Ouma, John H.; Wamachi, Alex; Kioko, John; Mungai, Peter; Njzovu, Malik; Kazura, James W.; King, Christopher L.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /09/2003 EN
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To determine whether maternal filariasis influences the risk of infection by and immunity to Wuchereria bancrofti in children, we performed a cross-sectional study in an area of Kenya where filariasis is endemic. Residents of 211 households were enrolled; 376 parents and 938 of their offspring between the ages of 2 and 17 years were examined for filarial infection status as determined by blood-borne microfilariae and filarial antigenemia. Children of infected mothers had a three- to fourfold increased risk of filarial infection, as ascertained by circulating filarial antigen, relative to children of uninfected mothers (P < 0.001). Paternal infection did not correlate with childhood infection status, indicating a specific maternal effect. Peripheral blood mononuclear cells from children of filaria-infected mothers (n = 33) had higher levels of constitutive interleukin-5 (IL-5) and IL-10, increased microfilarial antigen-specific IL-5 production, and diminished microfilarial antigen-driven lymphocyte proliferation than cells from children of uninfected mothers (n = 46; P < 0.05). In contrast, there were no differences between the two groups in adult worm antigen-driven gamma interferon, IL-2, IL-4, IL-5, and IL-10 production and lymphocyte proliferation. These data indicate that maternal filarial infection increases childhood susceptibility to W. bancrofti and skews filaria-specific immunity toward a Th2-type cytokine response. The results support the notion that in utero exposure to filarial antigens affects the natural history of filariasis during childhood.

Leukocyte Lactate Dehydrogenase Changes as an Indicator of Infection Prior to Overt Symptoms1

Leise, Esther M.; Gray, Irving; Ward, Martha K.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1968 EN
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66.90339%
Lactic acid dehydrogenase (LDH) concentration of rabbit serum and leukocytes was followed during the course of an acute infection with Diplococcus pneumoniae. Control values were obtained prior to infection, and again 4, 24, and 48 hr later. LDH isozymes were characterized by acrylamide gel electrophoresis and quantitated by densitometry. An increase in serum LDH was observed as early as 4 hr after infection. These levels returned to normal in 24 hr and rose again 48 hr after infection. The LDH level of leukocytes, from 10 of 12 infected rabbits, rose rapidly during the 24-hr period after exposure. The levels were two to three times the original preinoculation level for that animal. In six of these rabbits, this LDH elevation occurred 4 hr after inoculation and preceded the onset of fever. Change in the type of leukocyte did not account for the increase in cellular LDH. All infected rabbits showed approximately the same increase in polymorphonuclear leukocytes, but not all developed comparable increases in LDH. The isozyme patterns obtained, when defined amounts of enzyme were applied to the gel for electrophoresis, were characterized for the most part by a three-enzyme pattern. Increasing amounts of enzyme occasionally revealed a fourth...

Endotoxin-Induced Susceptibility to Staphylococcal Infection and Its Reversal by Adrenergic Blocking Agents1

Sultzer, Barnet M.; Freedman, Henry H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1965 EN
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76.86299%
Sultzer, Barnet M. (Princeton Laboratories, Inc., Princeton, N.J.), and Henry H. Freedman. Endotoxin-induced susceptibility to staphylococcal infection and its reversal by adrenergic blocking agents. J. Bacteriol. 90:1001–1006. 1965.—The transient phase of increased susceptibility to bacterial infection in mice provoked by prior administration of small doses of endotoxin was investigated for possible mediation by vasoactive substances. Animals were given endotoxin intravenously shortly before intraperitoneal injection of Staphylococcus aureus Smith, thereby lowering the lethal inoculum 10-fold. To determine whether this susceptibility state could be obviated, mice were pretreated with phenoxybenzamine or dibenzylchlorethylamine. Mortality decreased from an average of 81% in the endotoxin control groups to about 23% in the treated mice, closely approximating the mortality in control mice injected with saline and staphylococci. Neither antiadrenergic agent independently altered the resistance of mice to a higher lethal staphylococcal challenge, nor did these materials induce extravascular leukocyte mobilization into the peritoneal cavity. The results suggest a possible role of vasoactive staphylococcal α-toxin, as well as epinephrine or epinephrine-like factors...

Immunological Paralysis Against Type VIII and Immunity Against Type III Diplococcus pneumoniae Induced by the Soluble Specific Substance of Type VIII

Brooke, Marcus S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1965 EN
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76.877153%
Brooke, Marcus S. (Massachusetts Institute of Technology, Cambridge). Immunological paralysis against type VIII and immunity against type III Diplococcus pneumoniae induced by the soluble specific substance of type VIII. J. Bacteriol. 90:1296–1303. 1965.—Mice injected with relatively large quantities of the soluble specific substance of type VIII Diplococcus pneumoniae (SVIII) are, on the basis of challenge experiments, paralyzed against type VIII but immune against type III D. pneumoniae. Their sera contain antibodies which react with sheep cells coated with SIII. Unfortunately, it was not possible to develop an in vitro test with SVIII. When the SVIII was treated with a specific SVIII depolymerase before injection into mice, the sera still contained antibodies against SIII and some protection was afforded these mice against type III but not against type VIII challenge. When the SVIII was treated with a specific SIII depolymerase, antibodies were not detectable and the mice were not protected against type III or type VIII challenge. On the basis of these results it is suggested that either the SVIII strain is a hybrid forming both SVIII and SIII molecules or that part of the SVIII chain is altered to consist of repeating units of cellobiuronic acid rather than alternating units of cellobiuronic acid and the disaccharide galactose-glucose. The quantity of SIII in some preparations of SVIII is calculated to be of the order of 0.01%. It is not clear whether all type VIII strains at all times possess the capacity to elicit antibodies which react specifically against SIII...

STUDIES ON THE BLOOD PROTEINS : I. THE SERUM GLOBULINS IN BACTERIAL INFECTION AND IMMUNITY.

Hurwitz, S. H.; Meyer, K. F.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/11/1916 EN
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The progress of an infection is usually associated with marked changes in the serum proteins. There may be an increase in the percentage of the total protein during some stage of the infection, and there is usually a change in the albumin-globulin ratio with an increase in the total globulins. This rise may antedate the development of any resistance by a considerable period of time. The non-protein constituents of the blood show fluctuations with a tendency to rise as the infection progresses. The process of immunization is in almost all instances associated with a definite increase in the globulins of the blood, and in some cases with a complete inversion of the normal albumin-globulin ratio. This may be produced both by living and dead organisms and by bacterial endotoxins. Massive doses usually result in an upset which shows no tendency to right itself during the period of observation. A rise in the globulins has been shown to occur long before the animal develops immune bodies in any appreciable concentration; and where the globulin curve and antibody curve appear to parallel one another, it can be shown by a careful analysis of both curves that there is a definite lack of correspondence at various periods of the experiment. Animals possessing a basic immunity show a more rapid rise in the globulin curve following inoculation. There is no parallelism between the leukocytic reaction and the globulin reaction. During periods of leukopenia the globulins may be as high as during the period of a leukocytosis. Bacterial endotoxins produce as striking an increase in the serum globulins as do living and killed bacteria. This would seem to indicate that a bacterial invasion of the organism is not absolutely essential for the globulin changes...

Impaired Hepatitis C Virus (HCV)-Specific Effector CD8+ T Cells Undergo Massive Apoptosis in the Peripheral Blood during Acute HCV Infection and in the Liver during the Chronic Phase of Infection▿

Radziewicz, Henry; Ibegbu, Chris C.; Hon, Huiming; Osborn, Melissa K.; Obideen, Kamil; Wehbi, Mohammad; Freeman, Gordon J.; Lennox, Jeffrey L.; Workowski, Kimberly A.; Hanson, Holly L.; Grakoui, Arash
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
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66.952036%
A majority of patients infected with hepatitis C virus (HCV) do not sustain an effective T-cell response, and viremia persists. The mechanism leading to failure of the HCV-specific CD8+ T-cell response in patients developing chronic infection is unclear. We investigated apoptosis susceptibility of HCV-specific CD8+ T cells during the acute and chronic stages of infection. Although HCV-specific CD8+ T cells in the blood during the acute phase of infection and in the liver during the chronic phase were highly activated and expressed an effector phenotype, the majority was undergoing apoptosis. In contrast, peripheral blood HCV-specific CD8+ T cells during the chronic phase expressed a resting memory phenotype. Apoptosis susceptibility of HCV-specific CD8+ T cells was associated with very high levels of programmed death-1 (PD-1) and low CD127 expression and with significant functional T-cell deficits. Further evaluation of the “death phase” of HCV-specific CD8+ T cells during acute HCV infection showed that the majority of cells were dying by a process of cytokine withdrawal, mediated by activated caspase 9. Contraction during the acute phase occurred rapidly via this process despite the persistence of the virus. Remarkably, in the chronic phase of HCV infection...

Defining Postpartum Uterine Disease and the Mechanisms of Infection and Immunity in the Female Reproductive Tract in Cattle 1

Sheldon, I Martin; Cronin, James; Goetze, Leopold; Donofrio, Gaetano; Schuberth, Hans-Joachim
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
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67.26592%
Uterine microbial disease affects half of all dairy cattle after parturition, causing infertility by disrupting uterine and ovarian function. Infection with Escherichia coli, Arcanobacterium pyogenes and bovine herpesvirus 4 causes endometrial tissue damage. Toll-like receptors (TLRs) on endometrial cells detect pathogen-associated molecules such as bacterial DNA, lipids and lipopolysaccharide (LPS), leading to secretion of cytokines, chemokines and anti-microbial peptides. Chemokines attract neutrophils and macrophages to eliminate the bacteria, although persistence of neutrophils is associated with subclinical endometritis and infertility. Cows with uterine infections are less likely to ovulate because they have slower growth of the postpartum dominant follicle in the ovary, lower peripheral plasma estradiol concentrations, and perturbation of hypothalamic and pituitary function. The follicular fluid of animals with endometritis contains LPS, which is detected by the TLR4/CD14/LY96 (MD2) receptor complex on granulosa cells leading to lower aromatase expression and reduced estradiol secretion. If cows with uterine disease ovulate, the peripheral plasma concentrations of progesterone are lower than in normal animals. However luteal phases are often extended in animals with uterine disease...

Dynamics of Influenza Virus Infection and Pathology▿

Saenz, Roberto A.; Quinlivan, Michelle; Elton, Debra; MacRae, Shona; Blunden, Anthony S.; Mumford, Jennifer A.; Daly, Janet M.; Digard, Paul; Cullinane, Ann; Grenfell, Bryan T.; McCauley, John W.; Wood, James L. N.; Gog, Julia R.
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
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67.185723%
A key question in pandemic influenza is the relative roles of innate immunity and target cell depletion in limiting primary infection and modulating pathology. Here, we model these interactions using detailed data from equine influenza virus infection, combining viral and immune (type I interferon) kinetics with estimates of cell depletion. The resulting dynamics indicate a powerful role for innate immunity in controlling the rapid peak in virus shedding. As a corollary, cells are much less depleted than suggested by a model of human influenza based only on virus-shedding data. We then explore how differences in the influence of viral proteins on interferon kinetics can account for the observed spectrum of virus shedding, immune response, and influenza pathology. In particular, induction of high levels of interferon (“cytokine storms”), coupled with evasion of its effects, could lead to severe pathology, as hypothesized for some fatal cases of influenza.

Mycobacterium tuberculosis Promotes HIV trans-Infection and Suppresses Major Histocompatibility Complex Class II Antigen Processing by Dendritic Cells▿

Reuter, Morgan A.; Pecora, Nicole D.; Harding, Clifford V.; Canaday, David H.; McDonald, David
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.980244%
Mycobacterium tuberculosis is a leading killer of HIV-infected individuals worldwide, particularly in sub-Saharan Africa, where it is responsible for up to 50% of HIV-related deaths. Infection by HIV predisposes individuals to M. tuberculosis infection, and coinfection accelerates the progression of both diseases. In contrast to most other opportunistic infections associated with HIV, an increased risk of M. tuberculosis infection occurs during early-stage HIV disease, long before CD4 T cell counts fall below critical levels. We hypothesized that M. tuberculosis infection contributes to HIV pathogenesis by interfering with dendritic cell (DC)-mediated immune control. DCs carry pathogens like M. tuberculosis and HIV from sites of infection into lymphoid tissues, where they process and present antigenic peptides to CD4 T cells. Paradoxically, DCs can also deliver infectious HIV to T cells without first becoming infected, a process known as trans-infection. Lipopolysaccharide (LPS)-activated DCs sequester HIV in pocketlike membrane invaginations that remain open to the cell surface, and individual virions are delivered from the pocket into T cells at the site of contact during trans-infection. Here we report that M. tuberculosis exposure increases HIV trans-infection and induces viral sequestration within surface-accessible compartments identical to those seen in LPS-stimulated DCs. At the same time...

Vesicular Stomatitis Virus-Simian Retrovirus Type 2 Vaccine Protects Macaques from Detectable Infection and B-Cell Destruction▿†

Gautam, Rajeev; Iyer, Arun; Hunter, Meredith; Das, Arpita; Williams, Tessa; Dufour, Jason; Apetrei, Cristian; Kousoulas, K. Gus; Marx, Preston A.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /06/2011 EN
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66.916104%
Natural infection with simian retrovirus (SRV) has long been recognized in rhesus macaques (RMs) and may result in an AIDS-like disease. Importantly, SRV infections persist as a problem in recently imported macaques. Therefore, there is a clear need to control SRV spread in macaque colonies. We developed a recombinant vesicular stomatitis virus (VSV)-SRV vaccine consisting of replication-competent hybrid VSVs that express SRV gag and env in separate vectors. The goal of this study was to assess the immunogenicity and protective efficacy of the VSV-SRV serotype 2 vaccine prime-boost approach in RMs. The VSV-SRV vector (expressing either SRV gag or env) vaccines were intranasally administered in 4 RMs, followed by a boost 1 month after the first vaccination. Four RMs served as controls and received the VSV vector alone. Two months after the boost, all animals were intravenously challenged with SRV-2 and monitored for 90 days. After the SRV-2 challenge, all four controls became infected, and viral loads (VLs) ranged from 106 to 108 SRV RNA copies/ml of plasma. Two animals in the control group developed simian AIDS within 7 to 8 weeks postinfection and were euthanized. Anemia and weight loss were observed in the remaining controls. During acute infection...

Susceptibility to Acute Mouse Adenovirus Type 1 Respiratory Infection and Establishment of Protective Immunity in Neonatal Mice

Procario, Megan C.; Levine, Rachael E.; McCarthy, Mary K.; Kim, Eunnie; Zhu, Lingqiao; Chang, Cheong-Hee; Hershenson, Marc B.; Weinberg, Jason B.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /04/2012 EN
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67.18551%
There is an incomplete understanding of the differences between neonatal immune responses that contribute to the increased susceptibility of neonates to some viral infections. We tested the hypothesis that neonates are more susceptible than adults to mouse adenovirus type 1 (MAV-1) respiratory infection and are impaired in the ability to generate a protective immune response against a second infection. Following intranasal infection, lung viral loads were greater in neonates than in adults during the acute phase but the virus was cleared from the lungs of neonates as efficiently as it was from adult lungs. Lung gamma interferon (IFN-γ) responses were blunted and delayed in neonates, and lung viral loads were higher in adult IFN-γ−/− mice than in IFN-γ+/+ controls. However, administration of recombinant IFN-γ to neonates had no effect on lung viral loads. Recruitment of inflammatory cells to the airways was impaired in neonates. CD4 and CD8 T cell responses were similar in the lungs of neonates and adults, although a transient increase in regulatory T cells occurred only in the lungs of infected neonates. Infection of neonates led to protection against reinfection later in life that was associated with increased effector memory CD8 T cells in the lungs. We conclude that neonates are more susceptible than adults to acute MAV-1 respiratory infection but are capable of generating protective immune responses.

Utility of Humanized BLT Mice for Analysis of Dengue Virus Infection and Antiviral Drug Testing

Frias-Staheli, Natalia; Dorner, Marcus; Marukian, Svetlana; Billerbeck, Eva; Labitt, Rachael N.; Rice, Charles M.; Ploss, Alexander
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /02/2014 EN
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Dengue virus (DENV) is the cause of a potentially life-threatening disease that affects millions of people worldwide. The lack of a small animal model that mimics the symptoms of DENV infection in humans has slowed the understanding of viral pathogenesis and the development of therapies and vaccines. Here, we investigated the use of humanized “bone marrow liver thymus” (BLT) mice as a model for immunological studies and assayed their applicability for preclinical testing of antiviral compounds. Human immune system (HIS) BLT-NOD/SCID mice were inoculated intravenously with a low-passage, clinical isolate of DENV-2, and this resulted in sustained viremia and infection of leukocytes in lymphoid and nonlymphoid organs. In addition, DENV infection increased serum cytokine levels and elicited DENV-2-neutralizing human IgM antibodies. Following restimulation with DENV-infected dendritic cells, in vivo-primed T cells became activated and acquired effector function. An adenosine nucleoside inhibitor of DENV decreased the circulating viral RNA when administered simultaneously or 2 days postinfection, simulating a potential treatment protocol for DENV infection in humans. In summary, we demonstrate that BLT mice are susceptible to infection with clinical DENV isolates...

Statistics in Infection and Immunity Revisited

Olsen, Cara H.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /03/2014 EN
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66.935825%
In 2003, a review of the use of statistics in Infection and Immunity (IAI) found that more than half of articles had errors of statistical analysis or reporting of statistical results. This updated review of recent articles identifies and discusses the most common statistical methods reported in IAI and provides examples of both good reporting and common mistakes. Furthermore, it expands on the criteria for statistical analysis and reporting presented in the IAI “Instructions to Authors,” with the goal of helping both readers and authors better understand and apply the criteria.

Unraveling the Convoluted Biological Roles of Type I Interferons in Infection and Immunity: A Way Forward for Therapeutics and Vaccine Design

Wijesundara, Danushka Kumara; Xi, Yang; Ranasinghe, Charani
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 29/08/2014 EN
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66.94239%
It has been well-established that type I interferons (IFN-Is) have pleiotropic effects and play an early central role in the control of many acute viral infections. However, their pleiotropic effects are not always beneficial to the host and in fact several reports suggest that the induction of IFN-Is exacerbate disease outcomes against some bacterial and chronic viral infections. In this brief review, we probe into this mystery and try to develop answers based on past and recent studies evaluating the roles of IFN-Is in infection and immunity as this is vital for developing effective IFN-Is based therapeutics and vaccines. We also discuss the biological roles of an emerging IFN-I, namely IFN-ε, and discuss its potential use as a mucosal therapeutic and/or vaccine adjuvant. Overall, we anticipate the discussions generated in this review will provide new insights for better exploiting the biological functions of IFN-Is in developing efficacious therapeutics and vaccines in the future.

Impact of methamphetamine on infection and immunity

Salamanca, Sergio A.; Sorrentino, Edra E.; Nosanchuk, Joshua D.; Martinez, Luis R.
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 12/01/2015 EN
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The prevalence of methamphetamine (METH) use is estimated at ~35 million people worldwide, with over 10 million users in the United States. METH use elicits a myriad of social consequences and the behavioral impact of the drug is well understood. However, new information has recently emerged detailing the devastating effects of METH on host immunity, increasing the acquisition of diverse pathogens and exacerbating the severity of disease. These outcomes manifest as modifications in protective physical and chemical defenses, pro-inflammatory responses, and the induction of oxidative stress pathways. Through these processes, significant neurotoxicities arise, and, as such, chronic abusers with these conditions are at a higher risk for heightened consequences. METH use also influences the adaptive immune response, permitting the unrestrained development of opportunistic diseases. In this review, we discuss recent literature addressing the impact of METH on infection and immunity, and identify areas ripe for future investigation.