Host lung microbiota promotes malaria-associated acute respiratory distress syndrome

Author(s):Show less -

Mukherjee, Debanjan ; Chora, Angelo Ferreira ; Lone, Jean-Christophe ; Ramiro, Ricardo S. ; Blankenhaus, Birte ; Serre, Karine ; Ramirez, Mario ; Gordo, Isabel ; Veldhoen, Marc ; Varga-Weisz, Patrick ; Mota, Maria M.

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 13, n. 1, p. 14-pg., 2022-06-29.

Abstract

Severe malaria can manifest itself with a variety of well-recognized clinical phenotypes that are highly predictive of death - severe anaemia, coma (cerebral malaria), multiple organ failure, and respiratory distress. The reasons why an infected individual develops one pathology rather than another remain poorly understood. Here we use distinct rodent models of infection to show that the host microbiota is a contributing factor for the development of respiratory distress syndrome and host mortality in the context of malaria infections (malaria-associated acute respiratory distress syndrome, MA-ARDS). We show that parasite sequestration in the lung results in sustained immune activation. Subsequent production of the anti-inflammatory cytokine IL-10 by T cells compromises microbial control, leading to severe lung disease. Notably, bacterial clearance with linezolid, an antibiotic commonly used in the clinical setting to control lung-associated bacterial infections, prevents MA-ARDS-associated lethality. Thus, we propose that the host's anti-inflammatory response to limit tissue damage can result in loss of microbial control, which promotes MA-ARDS. This must be considered when intervening against life-threatening respiratory complications. The reasons why malaria manifests with a variety of well-recognized clinical phenotypes remain poorly understood. Here, using distinct rodent models, the authors reveal that the microbiota colonizing the lung promotes respiratory distress syndrome and mortality during malaria infections. (AU)

• FAPESP's process: 19/16113-5 - Chromatin dynamics in host-microbiome crosstalk in health and disease
• Grantee: Patrick Daniel Varga-Weisz
• Support Opportunities: Research Projects - SPEC Program