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Microbiota : understanding its role in the host-plasmodium affair
Publication . Mukherjee, Debanjan; Mota, Maria Manuel
The interplay between host and microbiota may define health or disease. Alterations in microbiota composition (mostly in the gut but also in other tissues) commonly referred to as ‘dysbiosis’ have been associated with a wide variety of disorders. However, the role the microbiota may play in malaria infections remains elusive. Here we show that host Plasmodium combinations leading to death due to malaria-associated acute respiratory distress syndrome (MA-ARDS) are associated with lung microbiota dysbiosis in mice. We further show that while host lung microbial dysbiosis contributes to MA-ARDS-induced death in mice, it has no impact on experimental cerebral malaria (eCM), a distinct malaria syndrome. Changes in lung microbiota result from parasite sequestration in the lungs and depend on IL-10 production by T cells. Notably, bacterial clearance using linezolid, an antibiotic used in the clinical setting to control lung-associated bacterial infections, prevented MA-ARDS (without affecting parasite load) but not eCM. These data show that Plasmodium infections can induce changes in host lung microbiota, which in turn promote malaria-associated severe disease and death. Thus, we propose that the host’s anti-inflammatory response to limit tissue damage can result in loss of microbial control and constitute a pathological self-amplifying cycle that must be considered when intervening against respiratory life-threatening complications.
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Fundação para a Ciência e a Tecnologia
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PD/BD/105836/2014