Cryptococcal pneumonia susceptibility in immunocompetent patients: Role of pseudomonas aeruginosa via IL-2/IL-12/IL-17 pathways.

BACKGROUND

While pulmonary cryptococcosis affects immunocompromised patients, it also occurs in immunocompetent individuals. However, underlying mechanisms contributing to susceptibility in immunocompetent patients remain poorly understood.

METHODS

We enrolled 43 patients with pulmonary cryptococcosis, including 19 apparently immunocompetent patients (ICPC) and 24 immunocompromised patients (IMCPC), compared with community-acquired pneumonia (CAP) controls. Bronchoalveolar lavage fluid (BLAF) microbiota composition was analyzed using metagenomic next-generation sequencing. Peripheral blood immune parameters were measured, and correlation analyses were performed to identify potential associations. Publicly available single-cell transcriptomic datasets were analyzed to explore immune pathway alterations associated with chronic Pseudomonas infection.

RESULTS

ICPC patients were predominantly male, less likely to present with fever, and showed normal inflammatory markers compared to CAP controls. Despite normal reference ranges, ICPC patients demonstrated significantly reduced CD4⁺ T lymphocyte percentages，accompanied by elevated IL-2 and reduced IL-12p70 and IL-17A levels. BALF analysis revealed a significant enrichment of nonfermenting gram-negative bacteria: Ralstonia, Sphingomonas, Acinetobacter, Stenotrophomonas, Burkholderi and Pseudomonas, in ICPC patients，whereas no such alterations were observed in the IMCPC group. Correlation analyses demonstrated inverse relationships between the relative abundances of Stenotrophomonas and Pseudomonas abundance and CD4 + T lymphocyte percentages and CD4 + /CD8 + ratios. Furthermore, single-cell transcriptomic analysis of chronic Pseudomonas infection showed enrichment of IL-2 signaling genes and suppression of IL-12 and IL-17A signaling pathways.

CONCLUSIONS

ICPC patients exhibit decreased peripheral CD4 + T lymphocyte percentage with elevated IL-2 and reduced IL-12p70/IL-17A levels. The observed enrichment of specific bacterial taxa, particularly Pseudomonas species, and its inverse correlation with immune parameters suggest potential microbiome-immune interactions that may contribute to cryptococcal susceptibility.