scholarly journals Role of Interleukin-4 (IL-4), IL-12, and Gamma Interferon in Primary and Vaccine-Primed Immune Responses to Friend Retrovirus Infection

2001 ◽  
Vol 75 (2) ◽  
pp. 654-660 ◽  
Author(s):  
Ulf Dittmer ◽  
Karin E. Peterson ◽  
Ron Messer ◽  
Ingunn M. Stromnes ◽  
Brent Race ◽  
...  
Keyword(s):  
Immune Responses ◽  
Gamma Interferon ◽  
Immunoglobulin M ◽  
Friend Virus ◽  
T Helper ◽  
Friend Retrovirus ◽  
Ifn Γ ◽  
Deficient Mice ◽  
Helper Type

ABSTRACT The immunological resistance of a host to viral infections may be strongly influenced by cytokines such as interleukin-12 (IL-12) and gamma interferon (IFN-γ), which promote T helper type 1 responses, and IL-4, which promotes T helper type 2 responses. We studied the role of these cytokines during primary and secondary immune responses against Friend retrovirus infections in mice. IL-4- and IL-12-deficient mice were comparable to wild-type B6 mice in the ability to control acute and persistent Friend virus infections. In contrast, more than one-third of the IFN-γ-deficient mice were unable to maintain long-term control of Friend virus and developed gross splenomegaly with high virus loads. Immunization with a live attenuated vaccine virus prior to challenge protected all three types of cytokine-deficient mice from viremia and high levels of spleen virus despite the finding that the vaccinated IFN-γ-deficient mice were unable to class switch from immunoglobulin M (IgM) to IgG virus-neutralizing antibodies. The results indicate that IFN-γ plays an important role during primary immune responses against Friend virus but is dispensable during vaccine-primed secondary responses.

Abstract 116: Detrimental Role of Toll-Like Receptor 4 in Cardiovirus-Induced Myocarditis

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Fumitaka Sato ◽  
Seiichi Omura ◽  
Nicholas E Martinez ◽  
Eiichiro Kawai ◽  
Ganta V Chaitanya ◽  
...  
Keyword(s):  
Immune Responses ◽  
Acute Phase ◽  
Viral Entry ◽  
Viral Myocarditis ◽  
Chronic Phase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tlr4 Ligand ◽  
Ifn Γ ◽  
Deficient Mice

Picornavirus infections have been known as a leading cause of viral myocarditis in humans. Theiler’s murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus, the family Picornaviridae and was reported to cause inflammation in the heart in one manuscript, while its pathomechanism is unclear. In viral myocarditis, viral replication in the heart and/or immune responses against virus as well as heart-antigen (autoimmunity) can contribute to the pathogenesis. Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) that are important for recognizing pathogens as well as triggering innate immunity. Among TLRs, TLR4 has been demonstrated to play important roles in virus-mediated pathology: 1) TLR4 can contribute to viral entry in some viruses, 2) TLR4 may mediate tissue damage by anti-virus immune responses (immunopathology), 3) high levels of TLR4 expression were observed in the heart of patients with dilated cardiomyopathy following acute viral myocarditis, and 4) some viruses can bind to lipopolysaccharide (LPS), which is a TLR4 ligand. To determine the role of TLR4 in TMEV-induced myocarditis, we infected male C3H/HeJ (TLR4-deficient) and C3H/HeNtac (control TLR4+) mice with the DA strain of TMEV. We harvested the hearts and spleens on days 6 and 7 (acute phase) or days 63 and 64 (chronic phase) post-infection. Cardiac pathology was evaluated by hematoxylin and eosin staining and production of pro-inflammatory cytokines, interleukin (IL)-17A and interferon (IFN)-γ, from spleen cells was measured by an enzyme-linked immunosorbent assay (ELISA). In both mice, mild myocarditis was observed during the acute phase of TMEV infection. During the chronic phase, both mice developed severe pathology in the heart, including basophilic degeneration and calcification. However, the incidence of myocarditis was higher in control mice than TLR4-deficient mice. IL-17A and IFN-γ production was higher in control mice than in TLR4-deficient mice (control vs. TLR4-deficient mice, acute phase: IL-17A, 196 vs. 146 pg/ml; IFN-γ, 72 vs. 39 ng/ml; chronic phase: IL-17A, 290 vs. 229 pg/ml; IFN- γ, 142 vs. 88 ng/ml). These results suggest that TLR4 may be detrimental in TMEV-induced myocarditis by increasing pro-inflammatory cytokine production.

scholarly journals Gamma Interferon Produced by Antigen-Specific CD4+ T Cells Regulates the Mucosal Immune Responses to Citrobacter rodentium Infection

2010 ◽  
Vol 78 (6) ◽  
pp. 2653-2666 ◽  
Author(s):  
Hideyuki Shiomi ◽  
Atsuhiro Masuda ◽  
Shin Nishiumi ◽  
Masayuki Nishida ◽  
Tetsuya Takagawa ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Gamma Interferon ◽  
Immune Defense ◽  
Interleukin 4 ◽  
Mucosal Inflammation ◽  
Citrobacter Rodentium ◽  
Macrophage Phagocytosis ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT Citrobacter rodentium, a murine model pathogen for enteropathogenic Escherichia coli, colonizes the surface of intestinal epithelial cells and causes mucosal inflammation. This bacterium is an ideal model for investigating pathogen-host immune interactions in the gut. It is well known that gene transcripts for Th1 cytokines are highly induced in colonic tissue from mice infected with C. rodentium. However, it remains to be seen whether the Th1 or Th2 cytokines produced by antigen-specific CD4+ T cells provide effective regulation of the host immune defense against C. rodentium infection. To investigate the antigen-specific immune responses, C. rodentium expressing ovalbumin (OVA-C. rodentium), a model antigen, was generated and used to define antigen-specific responses under gamma interferon (IFN-γ)-deficient or interleukin-4 (IL-4)-deficient conditions in vivo. The activation of antigen-specific CD4+ T cells and macrophage phagocytosis were evaluated in the presence of IFN-γ or IL-4 in vitro. IFN-γ-deficient mice exhibited a loss of body weight and a higher bacterial concentration in feces during OVA-C. rodentium infection than C57BL/6 (wild type) or IL-4-deficient mice. This occurred through the decreased efficiency of macrophage phagocytosis and the activation of antigen-specific CD4+ T cells. Furthermore, a deficiency in antigen-specific CD4+ T-cell-expressed IFN-γ led to a higher susceptibility to mucosal and gut-derived systemic OVA-C. rodentium infection. These results show that the IFN-γ produced by antigen-specific CD4+ T cells plays an important role in the defense against C. rodentium.

scholarly journals Friend virus limits adaptive cellular immune responses by imprinting a maturation-resistant and T helper type 2-biased immunophenotype in dendritic cells

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0192541 ◽  
Author(s):  
Limei Shen ◽  
Stefan Tenzer ◽  
Moritz Hess ◽  
Ute Distler ◽  
Ingrid Tubbe ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Friend Virus ◽  
T Helper ◽  
Cellular Immune Responses ◽  
Cellular Immune ◽  
Helper Type

scholarly journals Aberrant Contraction of Antigen-Specific CD4 T Cells after Infection in the Absence of Gamma Interferon or Its Receptor

2006 ◽  
Vol 74 (11) ◽  
pp. 6252-6263 ◽  
Author(s):  
Jodie S. Haring ◽  
John T. Harty
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Interleukin 2 ◽  
Gamma Interferon ◽  
Model Systems ◽  
Important Regulator ◽  
Ifn Γ ◽  
And Function ◽  
Deficient Mice

ABSTRACT Several lines of evidence from different model systems suggest that gamma interferon (IFN-γ) is an important regulator of T-cell contraction after antigen (Ag)-driven expansion. To specifically investigate the role of IFN-γ in regulating the contraction of Ag-specific CD4 T cells, we infected IFN-γ−/− and IFN-γR1−/− mice with attenuated Listeria monocytogenes and monitored the numbers of Ag-specific CD4 T cells during the expansion, contraction, and memory phases of the immune response to infection. In the absence of IFN-γ or the ligand-binding portion of its receptor, Ag-specific CD4 T cells exhibited normal expansion in numbers, but in both strains of deficient mice there was very little decrease in the number of Ag-specific CD4 T cells even at time points later than day 90 after infection. This significant delay in contraction was not due to prolonged infection, since mice treated with antibiotics to conclusively eliminate infection exhibited the same defect in contraction. In addition to altering the number of Ag-specific CD4 T cells, the absence of IFN-γ signaling also changed the phenotype of cells generated after infection. IFN-γR1−/− Ag-specific CD4 T cells reacquired expression of CD127 more quickly than wild-type cells, and more IFN-γR1−/− CD4 T cells were capable of producing both IFN-γ and interleukin 2 following Ag stimulation. From these data we conclude that IFN-γ regulates the contraction, phenotype, and function of Ag-specific CD4 T cells generated after infection.

scholarly journals The role of IL-5, IL-6 and IL-10 in primary and vaccine-primed immune responses to infection with Friend retrovirus (Murine leukaemia virus)

2001 ◽  
Vol 82 (6) ◽  
pp. 1349-1354 ◽  
Author(s):  
Beatrice D. Strestik ◽  
Anke R. M. Olbrich ◽  
Kim J. Hasenkrug ◽  
Ulf Dittmer
Keyword(s):  
Immune Responses ◽  
Viral Infections ◽  
Vaccine Virus ◽  
Live Attenuated Vaccine ◽  
Leukaemia Virus ◽  
Murine Leukaemia Virus ◽  
Friend Retrovirus ◽  
Suppressive Cytokine ◽  
Deficient Mice

The defence of a host against viral infections is strongly influenced by cytokines. We investigated the role of the B-cell stimulating cytokines IL-5 and IL-6, and the immuno-suppressive cytokine IL-10, during primary and secondary immune responses in mice against infection with Friend retrovirus (FV) (Murine leukaemia virus). IL-5−/− mice were comparable to C57BL/6 wild-type mice in their ability to control acute FV infection. In contrast, IL-6−/− and IL-10−/− mice showed significantly enhanced virus loads in spleen cells. However, this impaired control of acute FV replication did not alter the long-term control over persistent FV in IL-6−/− and IL-10−/− mice. Immunization with a live attenuated vaccine virus prior to challenge protected all three types of cytokine-deficient mice from high levels of spleen virus, despite the finding that the vaccinated IL-5- and IL-6-deficient mice had significantly reduced titres of virus-neutralizing IgG class antibodies. The results indicate that IL-6 and IL-10 contribute to primary immune responses against FV, but are dispensable during persistent infection and vaccine-primed secondary responses.

scholarly journals Gamma Interferon Dominates the Murine Cytokine Response to the Agent of Human Granulocytic Ehrlichiosis and Helps To Control the Degree of Early Rickettsemia

2000 ◽  
Vol 68 (4) ◽  
pp. 1827-1833 ◽  
Author(s):  
Mustafa Akkoyunlu ◽  
Erol Fikrig
Keyword(s):  
Gamma Interferon ◽  
Cytokine Response ◽  
Interleukin 4 ◽  
Infection Model ◽  
Granulocytic Ehrlichiosis ◽  
Human Granulocytic Ehrlichiosis ◽  
Ifn Γ ◽  
Immunocompetent Mice ◽  
Deficient Mice

ABSTRACT The cytokine response to the agent of human granulocytic ehrlichiosis (HGE) was assessed in a murine infection model and the role of gamma interferon (IFN-γ), a cytokine that is crucial for host defenses against intracellular pathogens, was investigated by using IFN-γ-deficient mice. The agent of HGE (aoHGE) is an obligate intracellular bacterium that survives within neutrophils: morulae (vacuoles containing HGE organisms) are evident in polymorphonuclear leukocytes of experimentally infected immunocompetent mice for 1 to 2 weeks. We now show that IFN-γ levels increase during early infection of C3H/HeN or C57BL/6 mice with HGE bacteria. Moreover, in response to aoHGE extracts or concanavalin A, splenocytes from ehrlichia-infected mice produced more IFN-γ and less interleukin-4 than controls, suggesting that aoHGE partially skewed the immune response towards a Th1 phenotype. Absolute concentration of morulae containing neutrophils in blood was 122 ± 22 cells/μl on day 8. The bacterial DNA burden was also highest on day 8 and then declined after IFN-γ levels peaked. In contrast, IFN-γ-deficient mice had a markedly elevated HGE bacteria burden with morulae concentration of 282 ± 48 cells/μl on day 5 (P = 0.004) and 242 ± 63 cells/μl on day 8 (P = 0.005). Rickettsemia resolved in immunocompetent and IFN-γ deficient mice after 2 weeks, while both the immunocompetent and the IFN-γ-deficient mice had increased serum antibodies against aoHGE antigens at this time point. These data demonstrate that the HGE agent elicits a prominent IFN-γ response in mice and that IFN-γ is important in controlling the degree of rickettsemia during the early phase of infection, while IFN-γ independent mechanisms play a role at later time points.

scholarly journals Role of Interleukin-18 in Host Defense against Disseminated Candida albicans Infection

2002 ◽  
Vol 70 (6) ◽  
pp. 3284-3286 ◽  
Author(s):  
Rogier J. L. Stuyt ◽  
Mihai G. Netea ◽  
Ineke Verschueren ◽  
Giamila Fantuzzi ◽  
Charles A. Dinarello ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Protective Effect ◽  
Host Defense ◽  
Gamma Interferon ◽  
Interleukin 18 ◽  
Ifn Γ ◽  
Candida Albicans Infection ◽  
Deficient Mice

ABSTRACT In mice injected intravenously with Candida albicans, administration of anti-interleukin-18 (IL-18) antibodies increased the yeast load in the kidneys. There was no effect on the organ load with Candida when gamma interferon (IFN-γ)-deficient mice were treated with anti-IL-18 antibodies, suggesting that the protective effect of IL-18 is mediated through endogenous IFN-γ.

scholarly journals Gamma Interferon Production by Cytotoxic T Lymphocytes Is Required for Resolution of Chlamydia trachomatis Infection

1998 ◽  
Vol 66 (11) ◽  
pp. 5457-5461 ◽  
Author(s):  
Mary F. Lampe ◽  
Christopher B. Wilson ◽  
Michael J. Bevan ◽  
Michael N. Starnbach
Keyword(s):  
Chlamydia Trachomatis ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Adoptive Transfer ◽  
Gamma Interferon ◽  
Chlamydia Trachomatis Infection ◽  
Immune Defect ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT In this study, we used mice in which the gene for gamma interferon (IFN-γ) has been disrupted (IFN-γ−/− mice) to study the role of this cytokine in the resolution of Chlamydia trachomatis infection. We show that IFN-γ−/− mice are impaired in the ability to clear infection with C. trachomatis compared to IFN-γ+/+ control mice. Activated CD8+ cytotoxic T lymphocytes (CTL) secrete IFN-γ in response to intracellular infection, and we have shown previously that a Chlamydia-specific CTL line can reduceC. trachomatis infection when adoptively transferred into infected mice. In the present study, we found that when these IFN-γ+/+ CTL lines are transferred intoChlamydia-infected IFN-γ−/− mice, the transferred CTL cannot overcome the immune defect seen in the IFN-γ−/− mice. We also show thatChlamydia-specific CTL can be cultured from IFN-γ-deficient mice infected with C. trachomatis; however, the adoptive transfer of IFN-γ−/− CTL into infected IFN-γ+/+ mice does not reduce the level of infection. These results suggest that IFN-γ production by CTL is not sufficient to overcome the defect that IFN-γ−/− mice have in the resolution of Chlamydia infection, yet IFN-γ production by CTL is required for the protective effect seen upon adoptive transfer of CTL into IFN-γ+/+ mice.

scholarly journals Increased Host Resistance against Pneumocystis carinii Pneumonia in γδ T-Cell-Deficient Mice: Protective Role of Gamma Interferon and CD8+ T Cells

2002 ◽  
Vol 70 (9) ◽  
pp. 5208-5215 ◽  
Author(s):  
Chad Steele ◽  
Mingquan Zheng ◽  
Erana Young ◽  
Luis Marrero ◽  
Judd E. Shellito ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Pneumocystis Carinii ◽  
Lavage Fluid ◽  
Gamma Interferon ◽  
Host Susceptibility ◽  
T Cell Subsets ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT Although a clear relationship between αβ T-cell receptor-positive (αβ-TCR+) CD4+ T cells and susceptibility to Pneumocystis carinii infection exists, the role of other T-cell subsets is less clearly defined. Previous studies have shown that γδ-TCR+ T cells infiltrate into the lung during P. carinii pneumonia. Therefore, the present study examined the role of γδ-TCR+ T cells in host defense against P. carinii pneumonia. C57BL/6 (control) and B6.129P2-Tcrdtm1Mom (γδ-TCR+ T-cell-deficient) mice were inoculated intratracheally with P. carinii. At specific time points, mice were sacrificed and analyzed for P. carinii burden, T-cell subsets, and cytokine levels in lung tissue. Analysis of P. carinii burden showed a more rapid and complete resolution of infection in γδ-TCR+ T-cell-deficient mice than in C57BL/6 controls. This augmented resolution was associated with elevated gamma interferon (IFN-γ) levels in bronchoalveolar lavage fluid predominantly produced by CD8+ T cells, as well as an increased recruitment of CD8+ T cells in general. In separate experiments, neutralization of IFN-γ or depletion of CD8+ T cells early during infection abolished the augmented resolution previously observed in γδ-TCR+ T-cell-deficient mice. These results show that the presence of γδ-TCR+ T cells modulates host susceptibility to P. carinii pneumonia through interactions with pulmonary CD8+ T cells and tissue production of IFN-γ.

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