Innate Immunity Acts as the Major Regulator in Talaromyces marneffei Coinfected AIDS Patients: Cytokine Profile Surveillance During Initial 6-Month Antifungal Therapy

Author:

Dong Rong-Jing1,Zhang Yun-Gui2,Zhu Lei1,Liu Heng-Li2,Liu Jun3,Kuang Yi-Qun4ORCID,Wang Rui-Rui5,Li Yu-Ye1

Affiliation:

1. Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China

2. Yunnan Provincial Hospital of Infectious Disease/AIDS Care Center (YNACC), Anning, China

3. Department of HIV/AIDS, The Third People’s Hospital of Kunming, Kunming, China

4. Institute of Infection and Immunology, Henan University and Center for Translational Medicine, Huaihe Clinical College, Huaihe Hospital of Henan University, Kaifeng, China

5. School of Pharmaceutial Sciences, Yunnan University of Traditional Chinese Medicine, Kunming, China

Abstract

Abstract Background Talaromycosis caused by Talaromyces marneffei infection is a fatal systemic mycosis in immunosuppressed individuals, such as patients with AIDS. Cytokines and immunocytes play a central role against fungus infection. However, how the host immune system responds to infection and treatment has not been reported to date. Methods Forty-one Talaromyces marneffei coinfected AIDS patients were followed up, their immunocytes and cytokine profiles were obtained at different antifungal treatment stages, and data on clinical features and laboratory examinations were collected. Correlation analysis was used to identify factors associated with host immunity against Talaromyces marneffei infection in AIDS patients. Results Common diseases and conditions of these 41 patients were lymphadenopathy, hepatomegaly, and splenomegaly. CD4+ T cells were extremely low in all of them. Moreover, significant increases of proinflammatory cytokines (IL-12, IL-17A, TNF-α, IFN-γ, IL-18, and IL-1β), anti-inflammatory cytokines (IL-10), and chemokines (IP-10) were observed in talaromycosis before treatment (P < .05), comparing to both AIDS patients and healthy controls. The cytokines IL-6, IL-8, TNF-α, IL-18, IL-17A, IL-7, IP-10, and IL-1β reached peak levels 3 days after initial antifungal therapy, and then gradually decreased. The symptoms of the patients gradually decreased. Furthermore, patients who died showed the highest levels of IL-6, TNF-α, IL-8, IL-1β, and IP-10, which were 1.4- to 164-fold higher than in surviving patients. Conclusions Our findings indicate that innate immune-cell-derived cytokines are critical for host defense against AIDS-associated Talaromyces marneffei infection; furthermore, excessive inflammatory cytokines are associated with poor outcomes.

Funder

National Science and Technology

National Natural Science Foundation of China

Joint Special Fund

Kunming Medical University

Science and Technology Innovation Team

Health and Family Planning Commission

Foundation of Health Technology

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Oncology

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