IL-10-/- Enhances DCs Immunity Against Chlamydia psittaci Infection via OX40L/NLRP3 and IDO/Treg Pathways.
Front Immunol
; 12: 645653, 2021.
Article
em En
| MEDLINE
| ID: mdl-34093535
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psitacose
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Células Dendríticas
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Interleucina-10
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Linfócitos T Reguladores
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Indolamina-Pirrol 2,3,-Dioxigenase
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Ligante OX40
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Proteína 3 que Contém Domínio de Pirina da Família NLR
Limite:
Animals
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China