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

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.

Extracellular Vesicles Derived From Talaromyces marneffei Yeasts Mediate Inflammatory Response in Macrophage Cells by Bioactive Protein Components

“…Oxidative stress was closely associated with inflammation response in regulating immune responses. In addition, the patients infected with TM have previously been reported to have higher TNF-α, IL-1β, IL-12, and IL-10 levels in vivo , and the infection of TM enabled the enhancement of the production of cytokines such as TNF-α, IL-1β, IL-6, and IL-12 by stimulating macrophages in vitro ( Dai et al, 2017 ; Dong et al, 2019 ). Therefore, a series of cytokines from macrophages was also measured, and the results have confirmed that EVs could enhance the secretion of IL-1β, IL-6, IL-10, and TNF-α in RAW264.7 macrophage cells, while there was no change in the IL-12 expression level.…”

Characterization of a novel yeast phase-specific antigen expressed during in vitro thermal phase transition of Talaromyces marneffei

“…We noted that the host phagocytes could mount an immune response to halt the progression of infection. In this regard, Dong et al recently demonstrated that the appropriate proinflammatory cytokines production in AIDS-associated talaromycosis plays a beneficial role in protective immunity and the survivability of patients 38 .…”

AIDS-associated Talaromyces marneffei central nervous system infection in patients of southwestern China

“…Talaromyces marneffei (T. marneffei, also known as Penicillium marneffei) is a regional opportunistic fungus that mainly causes life-threatening disseminated infection in acquired immunodeficiency syndrome (AIDS) that causes epidemics in southeast Asia [1] and south China [2,3]. It is estimated that approximately 50,000 HIV-positive patients are infected with T. marneffei every year in high-risk areas [4], and the incidence is likely to increase every year [5].…”