Interleukin-10 modulates antigen presentation by dendritic cells through regulation of NLRP3 inflammasome assembly during Chlamydia infection

Yusuf Omosun, Danielle McKeithen, Khamia Ryans, Caroline Kibakaya, Uriel Blas-Machado, Duo Li, Rajesh Singh, Koichi Inoue, Zhi Gang Xiong, Francis Eko, Carolyn Black, Joseph Igietseme, Qing He

Research output: Contribution to journalArticle

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Abstract

Interleukin-10 (IL-10) has been implicated in susceptibility to genital chlamydial infection and the development of tubal pathologies. IL-10 limitation also resulted in the rapid elicitation of immune responses against Chlamydia, and decreased levels of IL-10 correlated with protective anti-Chlamydia immunity. To investigate the molecular basis for these effects, we compared the reproductive pathologies and fertility rates in Chlamydia-infected wild-type (WT) and IL-10-knockout (IL-10-/-) mice; we also analyzed the expression of the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily, IL-1β production, NLRP3 inflammasome assembly and activation, and the immunostimulatory capacity and apoptotic predilection of Chlamydia-exposed dendritic cells (DCs) from WT and IL-10-/- mice. Our results revealed that, in addition to the rapid clearance of infection, genitally infected IL-10-/- mice were protected from tubal pathologies and infertility, whereas WT (IL-10+/+) mice were not. Chlamydia- pulsed IL-10-/- DCs expressed larger numbers of TLR4/IL-1R molecules and had enhanced IL-1β production. In addition, NLRP3 inflammasome assembly was suppressed in IL-10-/- DCs through the inhibition of the P2X purinoceptor 7 (P2X7) receptor (P2X7R), an ATP-gated ion channel, and a decrease in intracellular Ca2+ levels, which inhibited DC apoptosis. Thus, the potent immunostimulatory capacity of IL-10-deficient DCs is due, at least in part, to the suppression of the intracellular inflammasome assembly, which prevents DC apoptosis, allowing efficient antigen presentation. The results indicate that IL-10 deficiency enables efficient antigen presentation by DCs for rapid and enhanced immune activation against Chlamydia, which results in rapid microbial clearance, which prevents tubal pathologies during infection. Our finding has important implications for the induction of protective immunity against Chlamydia and other infectious and noninfectious diseases by vaccines.

Original languageEnglish (US)
Pages (from-to)4662-4672
Number of pages11
JournalInfection and Immunity
Volume83
Issue number12
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Inflammasomes
Chlamydia Infections
Antigen Presentation
Interleukin-10
Dendritic Cells
Chlamydia
Pathology
Interleukin-1 Receptors
Interleukin-1
Immunity
Purinergic P2X Receptors
Toll-Like Receptor 1
Infection
Apoptosis
Purinergic P2 Receptors
Birth Rate
Ion Channels
Knockout Mice
Infertility
Communicable Diseases

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Interleukin-10 modulates antigen presentation by dendritic cells through regulation of NLRP3 inflammasome assembly during Chlamydia infection. / Omosun, Yusuf; McKeithen, Danielle; Ryans, Khamia; Kibakaya, Caroline; Blas-Machado, Uriel; Li, Duo; Singh, Rajesh; Inoue, Koichi; Xiong, Zhi Gang; Eko, Francis; Black, Carolyn; Igietseme, Joseph; He, Qing.

In: Infection and Immunity, Vol. 83, No. 12, 01.01.2015, p. 4662-4672.

Research output: Contribution to journalArticle

Omosun, Y, McKeithen, D, Ryans, K, Kibakaya, C, Blas-Machado, U, Li, D, Singh, R, Inoue, K, Xiong, ZG, Eko, F, Black, C, Igietseme, J & He, Q 2015, 'Interleukin-10 modulates antigen presentation by dendritic cells through regulation of NLRP3 inflammasome assembly during Chlamydia infection', Infection and Immunity, vol. 83, no. 12, pp. 4662-4672. https://doi.org/10.1128/IAI.00993-15
Omosun, Yusuf ; McKeithen, Danielle ; Ryans, Khamia ; Kibakaya, Caroline ; Blas-Machado, Uriel ; Li, Duo ; Singh, Rajesh ; Inoue, Koichi ; Xiong, Zhi Gang ; Eko, Francis ; Black, Carolyn ; Igietseme, Joseph ; He, Qing. / Interleukin-10 modulates antigen presentation by dendritic cells through regulation of NLRP3 inflammasome assembly during Chlamydia infection. In: Infection and Immunity. 2015 ; Vol. 83, No. 12. pp. 4662-4672.
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AU - Blas-Machado, Uriel

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