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

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.

Clinical and chest computed tomography features associated with severe Chlamydia psittaci pneumonia diagnosed by metagenomic next-generation sequencing: A multicenter, retrospective, observational study

“…A persistent inflammatory response can lead to increased lymphocyte apoptosis and immunosuppression. [24][25][26][27][28] In summary, we believe that severe psittacosis pneumonia induces an excessive inflammatory response and immunosuppression in the early stage, and the lymphocyte counts and D-dimer, IL-2, IL-6, and IL-10 levels can help identify the severity of the disease.…”

Alternative strategies for Chlamydia treatment: Promising non-antibiotic approaches

“…In another study, the IL-10 level of patients with chlamydial infections was higher than that of uninfected individuals (Han et al, 2006 ). In a study on intranasal infection with C. psittaci , IL-10 −/− mice were found to promote activation and assembly of the NLRP3 inflammasome, promoting apoptosis, and leading to chlamydial clearance (Li Q. et al, 2021 ). Studies on mice with IL-10 deletion have shown that the loss of this cytokine distorts the anti-Chlamydial immune response, altering the dominant Th1 phenotype, and preventing Chlamydia -induced immunopathology (Bua et al, 2019 ; Sanchez et al, 2019 ).…”

TLR2 mediates autophagy through ERK signaling pathway in Chlamydia psittaci CPSIT_p7 protein‐stimulated RAW264.7 cells

“…Upon entering host cells, the EB differentiates into the RB and multiplies within a unique organelle called an inclusion. Furthermore, when RBs differentiate back into EBs, bacteria are released from host cells for transmission 4 . Although C. psittaci is a member of the Chlamydia genus, it has received less attention than other Chlamydia species in previous studies.…”

“…Furthermore, when RBs differentiate back into EBs, bacteria are released from host cells for transmission. 4 Although C. psittaci is a member of the Chlamydia genus, it has received less attention than other Chlamydia species in previous studies. C. psittaci can lead to respiratory disease in poultry and humans with various clinical signs, which is principally associated with avian chlamydiosis as a continuing risk to the health of humans and poultry.…”