IL-10-/- Enhances DCs Immunity Against Chlamydia psittaci Infection via OX40L/NLRP3 and IDO/Treg Pathways

Front Immunol. 2021 May 21:12:645653. doi: 10.3389/fimmu.2021.645653. eCollection 2021.

Abstract

Chlamydia psittaci (C. psittaci) is a common zoonotic agent that affects both poultry and humans. Interleukin 10 (IL-10) is an anti-inflammatory factor produced during chlamydial infection, while dendritic cells (DCs) are powerful antigen-presenting cells that induce a primary immune response in the host. However, IL-10 and DCs regulatory mechanisms in C. psittaci infection remain elusive. In vivo and in vitro investigations of the regulatory mechanisms were performed. IL-10-/- mice, conditional DCs depletion mice (zinc finger dendritic cell-diphtheria toxin receptor [zDC-DTR]), and double-deficient mice (DD, IL-10-/-/zDCDTR/DTR) were intranasally infected with C. psittaci. The results showed that more than 90% of IL-10-/- mice, 70% of wild-type mice, and 60% of double-deficient mice survived, whereas all zDC-DTR mice died. A higher lymphocyte proliferation index was found in the IL-10 inhibitor mice and IL-10-/- mice. Moreover, severe lesions and high bacterial loads were detected in the zDC-DTR mice compared with double-deficient mice. In vitro studies revealed increased OX40-OX40 ligand (OX40-OX40L) activation and CD4+T cell proliferation. Besides, the expression of indoleamine 2, 3-dioxygenase (IDO), and regulatory T cells were significantly reduced in the co-culture system of CD4+ T cells and IL-10-/- DCs in C. psittaci infection. Additionally, the activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome increased to facilitate the apoptosis of DCs, leading to rapid clearance of C. psittaci. Our study showed that IL-10-/- upregulated the function of deficient DCs by activating OX40-OX40L, T cells, and the NLPR3 inflammasome, and inhibiting IDO, and regulatory T cells. These effects enhanced the survival rate of mice and C. psittaci clearance. Our research highlights the mechanism of IL-10 interaction with DCs, OX40-OX40L, and the NLPR3 inflammasome, as potential targets against C. psittaci infection.

Keywords: Chlamydia psittaci; NLRP3 inflammasome; OX40-OX40L; apoptosis; dendritic cells; interleukin-10.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dendritic Cells / immunology*
  • Female
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / physiology*
  • Interleukin-10 / physiology*
  • Lung / microbiology
  • Lung / pathology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / physiology*
  • OX40 Ligand / physiology*
  • Psittacosis / immunology*
  • Psittacosis / mortality
  • Signal Transduction / physiology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • OX40 Ligand
  • Tnfsf4 protein, mouse
  • Interleukin-10