Early Induction of Gamma Interferon and Interleukin-10 Production in Draining Lymph Nodes from Mice Infected with<i>Borrelia burgdorferi</i>

Ganapamo, Frédéric; Dennis, Vida A.; Philipp, Mario T.

doi:10.1128/iai.68.12.7162-7165.2000

Cited by 29 publications

(45 citation statements)

References 21 publications

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“…IL-10 is known to suppress a number of different immune cell types, and its main biological role appears to involve reducing and eventually terminating inflammatory responses (61). M responses are potently suppressed by IL-10, and because M are believed to play a central role in both the innate and adaptive immune responses to B. burgdorferi, it is possible that M are better able to eradicate spirochetes in the absence of the substantial IL-10 amounts elicited in response to B. burgdorferi by B6 mice (60,62,63). Alternatively, our previous studies also showed that infected IL-10 Ϫ/Ϫ mice possessed significantly higher levels of B. burgdorferi-specific, as well as total, Ab levels compared with infected B6 mice (60), so it is possible that much of the increased clearance is mediated by this enhanced Ab response.…”

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confidence: 99%

IL-10 Deficiency Promotes Increased Borrelia burgdorferi Clearance Predominantly through Enhanced Innate Immune Responses

Lazarus

Meadows

Lintner

et al. 2006

The Journal of Immunology

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Borrelia burgdorferi is capable of persistently infecting a variety of hosts despite eliciting potent innate and adaptive immune responses. Preliminary studies indicated that IL-10-deficient (IL-10−/−) mice exhibit up to 10-fold greater clearance of B. burgdorferi from target tissues compared with wild-type mice, establishing IL-10 as the only cytokine currently known to have such a significant effect on spirochetal clearance. To further delineate these IL-10-mediated immune effects, kinetic studies indicated that spirochete dissemination to target tissues is similar in both wild-type and IL-10−/− mouse strains, and that enhanced clearance of B. burgdorferi in IL-10−/− mice is correlated with increased B. burgdorferi-specific Ab as early as 2 wk postinfection. Immunoblot analysis indicated that Abs produced by infected IL-10−/− and wild-type mice recognize similar ranges of spirochetal Ags. Immune sera from IL-10−/− and wild-type mice also exhibited similar bactericidal activity in vitro, and passive transfer of these immune sera into B. burgdorferi-infected SCID mice caused similar reductions of bacterial numbers in target tissues. Infectious dose studies indicated that 8-fold more B. burgdorferi were needed to efficiently infect naive IL-10−/− mice, suggesting these animals possess higher innate barriers to infection. Moreover, macrophages derived from IL-10−/− mice exhibit enhanced proinflammatory responses to B. burgdorferi stimulation compared with wild-type controls, and these responses are not significantly affected by the presence of immune serum. These findings confirm that B. burgdorferi clearance by innate immune responses is more efficient in the absence of IL-10, and these activities are not directly related to increased levels of B. burgdorferi-specific Ab.

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confidence: 99%

IL-10 Deficiency Promotes Increased Borrelia burgdorferi Clearance Predominantly through Enhanced Innate Immune Responses

Lazarus

Meadows

Lintner

et al. 2006

The Journal of Immunology

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“…There is evidence pointing to the importance of a T H 1/T H 2 balance, because increased IL-12 and T H 1-type cytokines are associated with disease progression in humans and susceptible strains of inbred mice (12)(13)(14)(15), whereas cytokines such as IL-10 have a beneficial effect (16)(17)(18)(19). In contrast, Bockenstedt et al (20) have shown that CD4 ϩ T H 1 cells were beneficial for the regression of carditis.…”

mentioning

confidence: 99%

NKT cells prevent chronic joint inflammation after infection withBorrelia burgdorferi

Tupin

Benhnia

Kinjo

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Borrelia burgdorferi is the etiologic agent of Lyme disease, a multisystem inflammatory disorder that principally targets the skin, joints, heart, and nervous system. The role of T lymphocytes in the development of chronic inflammation resulting from B. burgdorferi infection has been controversial. We previously showed that natural killer T (NKT) cells with an invariant (i) TCR ␣ chain (iNKT cells) recognize glycolipids from B. burgdorferi, but did not establish an in vivo role for iNKT cells in Lyme disease pathogenesis. Here, we evaluate the importance of iNKT cells for host defense against these pathogenic spirochetes by using V␣14i NKT cell-deficient (J␣18 ؊/؊ ) BALB/c mice. On tick inoculation with B. burgdorferi, J␣18 ؊/؊ mice exhibited more severe and prolonged arthritis as well as a reduced ability to clear spirochetes from infected tissues. V␣14i NKT cell deficiency also resulted in increased production of antibodies directed against both B. burgdorferi protein antigens and borrelial diacylglycerols; the latter finding demonstrates that anti-glycolipid antibody production does not require cognate help from V␣14i NKT cells. V␣14i NKT cells in infected wild-type mice expressed surface activation markers and produced IFN␥ in vivo after infection, suggesting a participatory role for this unique population in cellular immunity. Our data are consistent with the hypothesis that the antigen-specific activation of V␣14i NKT cells is important for the prevention of persistent joint inflammation and spirochete clearance, and they counter the long-standing notion that humoral rather than cellular immunity is sufficient to facilitate Lyme disease resolution.cytokines ͉ glycolipids ͉ Lyme disease ͉ spirochetes

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“…For example, modulation of IL-10 in vitro reciprocally influenced IFN-␥ production by stimulated synovial cells of Lyme arthritis patients (29). In addition, differences in IL-10-mediated regulation of IFN-␥ accounted for the differences in arthritic severity exhibited by C3H and C57BL/6 mice (3,28). In support of this, recent findings show that IL-10 plays a particularly important role in controlling the IFN-␥-driven arthritis caused, in large part, by CD4 ϩ T cells in B. burgdorferi-infected mice (30).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the effects of IL-10 on IL-17 production were more pronounced after 1 week of infection. Borrelial infection in the presence or absence of IL-10 may be associated with an inverse response of various inflammatory cytokines, including not only tumor necrosis factor alpha and IFN-␥ (3,4,(28)(29)(30)(46)(47)(48)(49)(50)(51) but also IL-17. If a certain threshold of immunosuppression by IL-10 is not achieved, a significant, multifaceted inflammatory response may ensue.…”

Section: Discussionmentioning

confidence: 99%

“…Early investigations into the differences in pathology observed between C3H and C57BL/6 mice demonstrated that the effect of IL-10 is a key factor in determining disease outcome (3,28). Until now, much of the investigation pertaining to the inflammatory targets of IL-10 focused on the Th1/IFN-␥ response, which has long been known as a major inflammatory pathway of later-stage Lyme arthritis (5,6).…”

Section: Discussionmentioning

confidence: 99%

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Interleukin-10 (IL-10) Inhibits Borrelia burgdorferi-Induced IL-17 Production and Attenuates IL-17-Mediated Lyme Arthritis

et al. 2013

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Previous studies have shown that cells and cytokines associated with interleukin-17 (IL-17)-driven inflammation are involved in the arthritic response to Borrelia burgdorferi infection. Here, we report that IL-17 is a contributing factor in the development of Lyme arthritis and show that its production and histopathological effects are regulated by interleukin-10 (IL-10). Spleen cells obtained from B. burgdorferi-infected, "arthritis-resistant" wild-type C57BL/6 mice produced low levels of IL-17 following stimulation with the spirochete. In contrast, spleen cells obtained from infected, IL-10-deficient C57BL/6 mice produced a significant amount of IL-17 following stimulation with B. burgdorferi. These mice developed significant arthritis, including erosion of the bones in the ankle joints. We further show that treatment with antibody to IL-17 partially inhibited the significant hind paw swelling and histopathological changes observed in B. burgdorferi-infected, IL-10-deficient mice. Taken together, these findings provide additional evidence of a role for IL-17 in Lyme arthritis and reveal an additional regulatory target of IL-10 following borrelial infection.

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Early Induction of Gamma Interferon and Interleukin-10 Production in Draining Lymph Nodes from Mice Infected withBorrelia burgdorferi

Cited by 29 publications

References 21 publications

IL-10 Deficiency Promotes Increased Borrelia burgdorferi Clearance Predominantly through Enhanced Innate Immune Responses

IL-10 Deficiency Promotes Increased Borrelia burgdorferi Clearance Predominantly through Enhanced Innate Immune Responses

NKT cells prevent chronic joint inflammation after infection withBorrelia burgdorferi

Interleukin-10 (IL-10) Inhibits Borrelia burgdorferi-Induced IL-17 Production and Attenuates IL-17-Mediated Lyme Arthritis

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