IFN-γ knockout mice show Th2-associated delayed-type hypersensitivity and the inflammatory cells fail to localize and control chlamydial infection

Wang, Shuhe; Fan, Yijun; Brunham, Robert C.; Yang, Xi

doi:10.1002/(sici)1521-4141(199911)29:11<3782::aid-immu3782>3.0.co;2-b

Cited by 122 publications

(107 citation statements)

References 35 publications

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“…Instead of mainly enhancing the differentiation and migration of neutrophils through induction of cytokines and chemokines, often seen in extracellular bacterial infections, IL-17/Th17 was found in the present study to be critically important for the development of type 1 responses of CD4 and CD8 T cells. Previous studies in our laboratory (23,24,40) and those of others (27,(41)(42)(43) have shown that Th1-type immune response induced by Cm infection is associated with protection against chlamydial infection. Our data in this study showed more severe infection and diseases in IL-17-neutralized mice, which correlated with reduced type 1 immune responses, including lower levels of Cm-driven IFN-␥ and local IL-12 production, and alteration of DC function.…”

Section: Discussionmentioning

confidence: 69%

“…Because previous studies have demonstrated the association of protection with type 1 T cell responses and more severe disease severity/ pathology with type 2 T cell responses (23,24,27), we further analyzed the Cm-driven type 1 and type 2 cytokine production by spleen and draining LN cells from the infected, IL-17-neutralized mice in comparison with the infected, sham-treated (IgG2a isotype control or PBS control) mice. The results showed that both spleen and LN cells isolated from IL-17-neutralized mice produced significantly lower levels of IFN-␥-and Th1-promoting cytokine (IL-12) than Mice were intranasally infected with 1 ϫ 10 3 IFUs of Cm.…”

Section: Il-17-neutralized Mice Exhibit Reduced Type 1 But Increasedmentioning

confidence: 99%

“…Chlamydia muridarum (Cm), a natural chlamydial strain of mouse, has been widely used in mouse models of respiratory and genital tract infections (22). Our and others' reported studies have shown that in respiratory tract chlamydial infection, type 1 CD4 and CD8 T cell immune responses, including IFN-␥ production, are critical for protection against chlamydial infection, whereas Th2-type immune responses are most likely associated with immunopathology (23)(24)(25)(26)(27). Therefore, it is important for a host to develop strong type 1 T cell immune responses for an efficient control of the infection and to prevent immunopathology.…”

mentioning

confidence: 99%

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IL-17/Th17 Promotes Type 1 T Cell Immunity against Pulmonary Intracellular Bacterial Infection through Modulating Dendritic Cell Function

Bai

Cheng

Gao

et al. 2009

The Journal of Immunology

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Although their contribution to host defense against extracellular infections has been well defined, IL-17 and Th17 are generally thought to have limited impact on intracellular infections. In this study, we investigated the role and mechanisms of IL-17/Th17 in host defense against Chlamydia muridarum, an obligate intracellular bacterium, lung infection. Our data showed rapid increase in IL-17 production and expansion of Th17 cells following C. muridarum infection and significant detrimental impact of in vivo IL-17 neutralization by anti-IL-17 mAb on disease course, immune response, and dendritic cell (DC) function. Specifically, IL-17-neutralized mice exhibited significantly greater body weight loss, higher organism growth, and much more severe pathological changes in the lung compared with sham-treated control mice. Immunological analysis showed that IL-17 neutralization significantly reduced Chlamydia-specific Th1 responses, but increased Th2 responses. Interestingly, the DC isolated from IL-17-neutralized mice showed lower CD40 and MHC II expression and IL-12 production, but higher IL-10 production compared with those from sham-treated mice. In two DC-T cell coculture systems, DC isolated from IL-17-neutralized mice induced higher IL-4, but lower IFN-γ production by Ag-specific T cells than those from sham-treated mice in cell priming and reaction settings. Adoptive transfer of DC isolated from IL-17-neutralized mice, unlike those from sham-treated mice, failed to protect the recipients against challenge infection. These findings provide in vivo evidence that IL-17/Th17 plays an important role in host defense against intracellular bacterial infection, and suggest that IL-17/Th17 can promote type 1 T cell immunity through modulating DC function.

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Section: Discussionmentioning

confidence: 69%

Section: Il-17-neutralized Mice Exhibit Reduced Type 1 But Increasedmentioning

confidence: 99%

mentioning

confidence: 99%

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IL-17/Th17 Promotes Type 1 T Cell Immunity against Pulmonary Intracellular Bacterial Infection through Modulating Dendritic Cell Function

Bai

Cheng

Gao

et al. 2009

The Journal of Immunology

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146

164

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show abstract

“…Previous studies by our and other groups have shown that respiratory tract C. muridarum (MoPn) infection induces predominant Th1-like immune responses [22,23]. Recent studies showed that adoptively transferred DC pulsed with nonviable chlamydial organisms induced Chlamydia-specific Th1 immune responses, which were equally protective as live chlamydial immunization [24].…”

Section: Introductionmentioning

confidence: 99%

Dendritic cells from Chlamydia‐infected mice show altered Toll‐like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin

et al. 2004

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Our previous study has shown that Chlamydia lung infection can inhibit local eosinophilic inflammation induced by allergen sensitization and challenge, which is correlated with altered cytokine production. In the present study, we examined the role played by dendritic cells (DC) in chlamydial infection-mediated modulation of allergic responses. The results showed that DC freshly isolated from Chlamydia-infected mice (iIDC), unlike those from naive control mice (iNDC), could efficiently modulate immune responses to ovalbumin in vitro and in vivo. Co-culture of freshly isolated DC with naive CD4 cells from T cell receptor transgenic mice (DO11.10) showed that iIDC directed Th1-dominant, while iNDC directed Th2-dominant, allergen-specific CD4 T cell responses. Moreover, adoptive transfer of iIDC, but not iNDC, could inhibit systemic and local eosinophilia induced by allergen exposure. The reduction of eosinophilia was associated with a decrease in IL-5 receptor expression on bone marrow cells and the production of IL-5 and IL-13 by T lymphocytes. Analysis of the DC showed that iIDC expressed significantly higher levels of mRNA for Toll-like receptor 9 and produced more IL-12 compared to iNDC. The data demonstrate a critical role played by DC in infection-mediated inhibition of allergic responses.

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“…IFN-+ gene knockout (IFN-+ -/-) mice, IFN-+ receptor gene knockout (IFN-+ R -/-) mice, as well as other IFN-+ -related gene knockout mice are extremely susceptible to intracellular pathogens compared to SCID or wild-type (WT) mice [5][6][7][8][9][10][11][12][13]. Whereas NK cells among lymphoid cells had been believed to be a major source of IFN-+ during early phase of infection, we and others have shown that antigen-presenting cells (APC) such as dendritic cells (DC) and macrophages produce large amounts of IFN-+ in response to interleukin (IL)-12 that is produced by APC upon microbial infection [14][15][16][17][18][19][20][21][22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

In vivo role of IFN‐γ produced by antigen‐presenting cells in early host defense against intracellular pathogens

et al. 2003

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Antigen-presenting cells (APC), including dendritic cells and macrophages, produce a large amount of interferon (IFN)-+ , a crucial cytokine for the control of infectious diseases. To elucidate the role of IFN-+ from APC in vivo, we employed cytokine receptor common + subunit ( + c) and recombination-activating gene (Rag)-2 double-knockout ( + c -/-(y) -Rag-2 -/-) mice, which are severely impaired in IFN-+ production and are extremely susceptible to infection of intracellular pathogens including Listeria monocytogenes and Toxoplasma gondii. Adoptive transfer of IFN-+ -producing APC increased levels of serum IFN-+ and the resistance to Listeria. Although depletion of NK cells from Rag-2 -/-mice slightly increased the susceptibility to bacterial infection, they are substantially more resistant than + c -/-(y) -Rag-2 -/-mice, which are also devoid of all lymphoid cells. These results demonstrate that the APC-derived IFN-+ contributes to the control of infectious agents in vivo.

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IFN-γ knockout mice show Th2-associated delayed-type hypersensitivity and the inflammatory cells fail to localize and control chlamydial infection

Cited by 122 publications

References 35 publications

IL-17/Th17 Promotes Type 1 T Cell Immunity against Pulmonary Intracellular Bacterial Infection through Modulating Dendritic Cell Function

IL-17/Th17 Promotes Type 1 T Cell Immunity against Pulmonary Intracellular Bacterial Infection through Modulating Dendritic Cell Function

Dendritic cells from Chlamydia‐infected mice show altered Toll‐like receptor expression and play a crucial role in inhibition of allergic responses to ovalbumin

In vivo role of IFN‐γ produced by antigen‐presenting cells in early host defense against intracellular pathogens

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