Antibody, but not B‐cell–dependent antigen presentation, plays an essential role in preventing <i>Chlamydia</i> systemic dissemination in mice

Malaviarachchi, Priyangi A.; Mercado, Miguel A.B.; McSorley, Stephen J.; Li, Lin-Xi

doi:10.1002/eji.201948391

Cited by 12 publications

(7 citation statements)

References 58 publications

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“…Circulating immunity induced after IN immunization consisted of both antigen-specific CD4 T cells and IgG antibodies, and recent studies point to an important role for antibody in Chlamydia protection (20,21). Local secretion of Cm-specific IgG was detected in the FRT after IN immunization, and the injection of serum into the vaginal vault efficiently blocked infection.…”

Section: Discussionmentioning

confidence: 98%

Circulating immunity protects the female reproductive tract from Chlamydia infection

Labuda

Pham

Depew

et al. 2021

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

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Anatomical positioning of memory lymphocytes within barrier tissues accelerates secondary immune responses and is thought to be essential for protection at mucosal surfaces. However, it remains unclear whether resident memory in the female reproductive tract (FRT) is required for Chlamydial immunity. Here, we describe efficient generation of tissue-resident memory CD4 T cells and memory lymphocyte clusters within the FRT after vaginal infection with Chlamydia. Despite robust establishment of localized memory lymphocytes within the FRT, naïve mice surgically joined to immune mice, or mice with only circulating immunity following intranasal immunization, were fully capable of resisting Chlamydia infection via the vaginal route. Blocking the rapid mobilization of circulating memory CD4 T cells to the FRT inhibited this protective response. These data demonstrate that secondary protection in the FRT can occur in the complete absence of tissue-resident immune cells. The ability to confer robust protection to barrier tissues via circulating immune memory provides an unexpected opportunity for vaccine development against infections of the FRT.

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Section: Discussionmentioning

confidence: 98%

Circulating immunity protects the female reproductive tract from Chlamydia infection

Labuda

Pham

Depew

et al. 2021

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

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“…Thus, functioning MHC class-II restricted CD4 T cell responses are the primary requirement for bacterial clearance. In marked contrast, gene-deficient mice lacking MHC class-I or B cells resolve primary Chlamydia infection [ 13 , 17 ], although systemic infection has been detected in B cell-deficient mice before clearance occurs [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Th1 cells are dispensable for primary clearance of Chlamydia from the female reproductive tract of mice

2022

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Protective immune responses to Chlamydia infection within the female reproductive tract (FRT) are incompletely understood. MHC class II-restricted CD4 Th1 responses are believed to be vital for bacterial clearance due to their capacity to secrete IFN-γ, but an essential requirement for T-bet-expressing Th1 cells has yet to be demonstrated in the mouse model of Chlamydia infection. Here, we investigated the role of T-bet and IFN-γ in primary clearance of Chlamydia after FRT infection. Surprisingly, IFN-γ producing CD4 T cells from the FRT expressed low levels of T-bet throughout infection, suggesting that classical T-bet-expressing Th1 cells are inefficiently generated and therefore unlikely to participate in bacteria clearance. Furthermore, mice deficient in T-bet expression or with a CD4-specific T-bet deficiency cleared FRT infection similarly to wild-type controls. T-bet-deficient mice displayed significant skewing of FRT CD4 T cells towards Th17 responses, demonstrating that compensatory effector pathways are generated in the absence of Th1 cells. In marked contrast, IFN-γ-, and IFN-γR-deficient mice were able to reduce FRT bacterial burdens, but suffered systemic bacterial dissemination and 100% mortality. Together, these data demonstrate that IFN-γ signaling is essential to protect mice from fatal systemic disease, but that classical T-bet-expressing Th1 cells are non-essential for primary clearance within the FRT. Exploring the protective contribution of Th1 cells versus other CD4 effector lineages could provide important information for the generation of new Chlamydia vaccines.

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“…PmpD is an attractive vaccine candidate for the prevention of Ct infections due to its interstrain conserved nature, surface localization, implications in early host-cell interaction, and immunological importance because it is the target of neutralizing antibodies 9 , 12 , 13 . As previously shown, antibodies essentially contribute to the resolution of primary Ct infections, and prevent bacterial systemic dissemination in mice 14 , 15 . Furthermore, studies from antibody-deficient mice revealed the fundamental role played by the humoral immune response in conferring protection against chlamydial genital tract re-infection 16 , 17 .…”

Section: Introductionmentioning

confidence: 62%

Heterologous prime-boost vaccination based on Polymorphic protein D protects against intravaginal Chlamydia trachomatis infection in mice

Russi

Balzo

Lujan

et al. 2022

Sci Rep

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The control of the worldwide spread of sexually transmitted Chlamydia trachomatis (Ct) infection urgently demands the development of a preventive vaccine. In this work, we designed a vaccine based on a fragment of polymorphic protein D (FPmpD) that proved to be immunogenic enough to generate a robust systemic and mucosal IgG humoral immune response in two strains of mice. We used a heterologous prime-boost strategy, including simultaneous systemic and mucosal administration routes. The high titers of anti-PmpD antibodies elicited by this immunization scheme did not affect murine fertility. We tested the vaccine in a mouse model of Ct intravaginal infection. Anti-PmpD antibodies displayed potent neutralizing activity in vitro and protective effects in uterine tissues in vivo. Notably, the humoral immune response of PmpD-vaccinated mice was faster and stronger than the primary immune response of non-vaccinated mice when exposed to Ct. FPmpD-based vaccine effectively reduced Ct shedding into cervicovaginal fluids, bacterial burden at the genitourinary tract, and overall infectivity. Hence, the FPmpD-based vaccine might constitute an efficient tool to protect against Ct intravaginal infection and decrease the infection spreading.

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Antibody, but not B‐cell–dependent antigen presentation, plays an essential role in preventing Chlamydia systemic dissemination in mice

Cited by 12 publications

References 58 publications

Circulating immunity protects the female reproductive tract from Chlamydia infection

Circulating immunity protects the female reproductive tract from Chlamydia infection

Th1 cells are dispensable for primary clearance of Chlamydia from the female reproductive tract of mice

Heterologous prime-boost vaccination based on Polymorphic protein D protects against intravaginal Chlamydia trachomatis infection in mice

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