AIDS patients with Talaromycosis Marneffei exhibit inflammatory activation and depletion in their peripheral blood monocytes

OBJECTIVES: This study seeks to investigate the characteristics, dynamics, and association with disease progression of monocyte inflammation in patients with AIDS/Talaromycosis Marneffei (TSM). The findings are expected to contribute to a deeper understanding of the disease's pathogenesis and prognostic factors, offering substantial potential for advancing diagnostic and therapeutic approaches and identifying new targets for immunotherapy. METHODS: We conducted a cross-sectional study to compare individuals with AIDS/TSM to those with AIDS/Pneumocystis Pneumonia(PCP), AIDS/tuberculosis(TB), uncomplicated AIDS, and healthy controls by analyzing the ratios and absolute values of peripheral blood mononuclear cells. Correlation analyses were employed to elucidate the relationship between monocyte levels and disease progression and prognosis. Flow cytometry and transcriptome sequencing were utilized to characterize the monocytes in patients with AIDS/TSM. Subsequently, a prospective study was undertaken on the TSM cohort to observe changes in monocyte numbers and proportions. RESULTS: We observed a significant reduction in both the number and proportion of these cells in TSM patients. This reduction was correlated with disease progression indicators such as platelet count (PLT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin (ALB). Furthermore, the baseline absolute monocyte count was found to be a significant predictor of mortality. Utilizing flow cytometry to analyze monocyte subpopulations, we found that the decrease in monocytes in TSM patients was characterized by an increase in classical monocytes and a decrease in intermediate and non-classical monocytes. Transcriptome sequencing data of monocytes revealed that those in TSM patients exhibited inflammatory activation, which was more pronounced in patients who succumbed to the disease. Subsequently, we conducted a prospective study on the TSM cohort and observed that antifungal treatment led to a gradual normalization of monocyte numbers and proportions. CONCLUSIONS: The peripheral blood monocytes of patients with AIDS and TSM exhibit a significant reduction, which correlates with disease progression and prognosis. Furthermore, these mononuclear cells demonstrate signs of inflammatory activation alongside a quantitative depletion.