# Cytokine Profile and Oxidative Patterns in Murine Models of Disseminated Infection by Mucorales Species

## TL;DR

This study explores how different Mucorales fungi trigger immune responses in mice, revealing that the spleen plays a central role in coordinating these reactions.

## Contribution

The study identifies species-specific immune dynamics and the spleen's role in mucormycosis, expanding understanding beyond immunosuppression.

## Key findings

- R. oryzae caused the strongest inflammatory response, with peak IL-17A levels on day 7.
- M. circinelloides triggered the highest TNF-α levels on day 3, while R. pusillus showed early but moderate inflammation.
- IL-10 negatively regulated inflammation, while TNF-α and IL-17A correlated with infection intensity.

## Abstract

Mucormycosis is a life-threatening infection caused by fungi of the Mucorales order, typically associated with immunocompromised hosts, but increasingly reported in immunocompetent individuals. This study investigated fungal burden, Th1/Th17 inflammatory profiles, and organ-specific dynamics in immunocompetent BALB/c mice intravenously infected with Rhizopus oryzae, Mucor circinelloides, or Rhizomucor pusillus. Colony-forming units were quantified in spleen, liver, and kidney at multiple time points, while serum cytokines and oxidative stress markers were analyzed. The results showed fungal persistence primarily in the spleen, accompanied by species-specific Th1/Th17 responses: R. oryzae induced the highest inflammatory response among all groups, with maximal cytokine production observed on day 7, particularly for IL-17A (352.58 pg/mL). In contrast, M. circinelloides exhibited its peak cytokine levels earlier, reaching the highest TNF-α concentration on day 3 (425.43 pg/mL). Meanwhile, R. pusillus triggered an early but moderate inflammatory response, with a maximum TNF-α value of 372.62 pg/mL detected on day 1, followed by clearance. Correlation analysis highlighted distinct immunological patterns, with IL-10 acting as a negative regulator of inflammation, while TNF-α and IL-17A reflected infection intensity depending on species and timing. The spleen emerged as a key organ coordinating immune responses during systemic infection. These findings reveal that mucormycosis in immunocompetent hosts triggers complex, species-dependent immune dynamics beyond classical immunosuppression, emphasizing the need to consider host–pathogen interactions when developing targeted antifungal strategies.