The Complement C3a Receptor Is Critical in Defense against Chlamydia psittaci in Mouse Lung Infection and Required for Antibody and Optimal T Cell Response

Dutow, Pavel; Fehlhaber, Beate; Bode, Jenny; Laudeley, Robert; Rheinheimer, Claudia; Glage, Silke; Wetsel, Rick A.; Pabst, Oliver; Klos, Andreas

doi:10.1093/infdis/jit640

Cited by 39 publications

(32 citation statements)

References 44 publications

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“…Thus, C3aR protects the host against listeriosis by inhibiting splenocyte death. A similar phenotype was recently described in C3aR−/− mice infected with the intracellular bacterium Chlamydia psittaci (Dutow et al, 2014). C3aR−/− mice were more susceptible to pulmonary C. psittaci infections and had significantly fewer T cells and B cells in their draining lymph nodes than WT mice.…”

Section: Role Of the C3a And C5a Receptors In Listeriosissupporting

confidence: 80%

Innate and adaptive immunologic functions of complement in the host response to Listeria monocytogenes infection

2016

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Listeria monocytogenes is a leading cause of foodborne-illness associated mortality that has attracted considerable attention in recent years due to several significant outbreaks. It has also served as a model organism for the study of intracellular pathogens. For these reasons the host response to L. monocytogenes has long been the subject of investigation. A potent innate and adaptive immune response is required for containment and clearance of L. monocytogenes. However, some elements of this response, such as type 1 interferons, can be detrimental to the host. Recent studies have revealed novel functions for the complement system, an ancient arm of innate immunity, in this process. Here we review the role of complement in the host response to L. monocytogenes.

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Section: Role Of the C3a And C5a Receptors In Listeriosissupporting

confidence: 80%

Innate and adaptive immunologic functions of complement in the host response to Listeria monocytogenes infection

2016

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“…Interestingly, the complement antichlamydial activity seemed to depend on the early complement components, such as C3, but not late components, including C5 (32). Consistent with these earlier observations are the recent findings that mice deficient in C3 or C3aR, but not C5, displayed drastically increased susceptibility to airway infection with Chlamydia psittaci (33,34). However, the role of the complement system or C5a in chlamydial induction of hydrosalpinx remains unknown.…”

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confidence: 75%

Complement Factor C5 but Not C3 Contributes Significantly to Hydrosalpinx Development in Mice Infected with Chlamydia muridarum

et al. 2014

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bHydrosalpinx is a pathological hallmark of tubal infertility associated with chlamydial infection. However, the mechanisms of hydrosalpinx remain unknown. Here, we report that complement factor 5 (C5) contributes significantly to chlamydial induction of hydrosalpinx. Mice lacking C5 (C5 ؊/؊ ) failed to develop any hydrosalpinx, while ϳ42% of the corresponding wild-type mice (C5 ؉/؉ ) did so following intravaginal infection with Chlamydia muridarum. Surprisingly, deficiency in C3 (C3 ؊/؊ ), an upstream component of the complement system, did not affect mouse susceptibility to chlamydial induction of hydrosalpinx. Interestingly, C5 activation was induced by chlamydial infection in oviducts of C3 ؊/؊ mice, explaining why the C3 ؊/؊ mice remained susceptible to chlamydial induction of hydrosalpinx. Similar levels of live chlamydial organisms were recovered from oviduct tissues of both C5 ؊/؊ and C5 ؉/؉ mice, suggesting that C5 deficiency did not affect C. muridarum ascending infection. Furthermore, C5؊/؊ mice were still more resistant to hydrosalpinx induction than C5 ؉/؉ mice, even when live C. muridarum organisms were directly delivered into the upper genital tract, both confirming the role of C5 in promoting hydrosalpinx and indicating that the C5-facilitated hydrosalpinx was not due to enhancement of ascending infection. The C5 ؊/؊ mice displayed significantly reduced lumenal inflammatory infiltration and cytokine production in oviduct tissue, suggesting that C5 may contribute to chlamydial induction of hydrosalpinx by enhancing inflammatory responses.

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“…Indeed, C3aR, but not C5aR, was found recently to be required for specific CD4 ϩ and CD8 ϩ T cell responses in lungdraining lymph nodes and critical for mouse survival during Chlamydia psittaci infections. It remains to be determined whether C3a was acting on the T cells directly or indirectly via APCs [38,39]. Interestingly, another study investigating the role of C3 (but not specific C3 fragments) found that during primary Listeria monocytogenes infection, a lack of C3 dramatically reduces the proliferation of CD4 ϩ and CD8 ϩ T cells.…”

Section: Complement Component C3mentioning

confidence: 99%

Complement modulation of T cell immune responses during homeostasis and disease

Clarke

Tenner

2014

Journal of Leukocyte Biology

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The complement system is an ancient and critical effector mechanism of the innate immune system as it senses, kills, and clears infectious and/or dangerous particles and alerts the immune system to the presence of the infection and/or danger. Interestingly, an increasing number of reports have demonstrated a clear role for complement in the adaptive immune system as well. Of note, a number of recent studies have identified previously unknown roles for complement proteins, receptors, and regulators in T cell function. Here, we will review recent data demonstrating the influence of complement proteins C1q, C3b/iC3b, C3a (and C3aR), and C5a (and C5aR) and complement regulators DAF (CD55) and CD46 (MCP) on T cell function during homeostasis and disease. Although new concepts are beginning to emerge in the field of complement regulation of T cell function, future experiments should focus on whether complement is interacting directly with the T cell or is having an indirect effect on T cell function via APCs, the cytokine milieu, or downstream complement activation products. Importantly, the identification of the pivotal molecular pathways in the human systems will be beneficial in the translation of concepts derived from model systems to therapeutic targeting for treatment of human disorders.

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The Complement C3a Receptor Is Critical in Defense against Chlamydia psittaci in Mouse Lung Infection and Required for Antibody and Optimal T Cell Response

Cited by 39 publications

References 44 publications

Innate and adaptive immunologic functions of complement in the host response to Listeria monocytogenes infection

Innate and adaptive immunologic functions of complement in the host response to Listeria monocytogenes infection

Complement Factor C5 but Not C3 Contributes Significantly to Hydrosalpinx Development in Mice Infected with Chlamydia muridarum

Complement modulation of T cell immune responses during homeostasis and disease

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