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Host lung microbiota promotes malaria-associated acute respiratory distress syndrome

Mukherjee, Debanjan and Chora, Ângelo Ferreira and Lone, Jean-Christophe and Ramiro, Ricardo S and Blankenhaus, Birte and Serre, Karine and Ramirez, Mário and Gordo, Isabel and Veldhoen, Marc and Varga-Weisz, Patrick and Mota, Maria M (2022) 'Host lung microbiota promotes malaria-associated acute respiratory distress syndrome.' Nature Communications, 13 (1). ISSN 2041-1723

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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.

Item Type: Article
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 13 Jul 2022 12:10
Last Modified: 23 Sep 2022 19:54
URI: http://repository.essex.ac.uk/id/eprint/33135

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