Acute lung injury is prevented by monocyte locomotion inhibitory factor in an experimental severe malaria mouse model.

Acute lung injury caused by severe malaria (SM) is triggered by a dysregulated immune response towards the infection with Plasmodium parasites. Postmortem analysis of human lungs shows diffuse alveolar damage (DAD), the presence of CD8 lymphocytes, neutrophils, and increased expression of Intercellular Adhesion Molecule 1 (ICAM-1). P. berghei ANKA (PbA) infection in C57BL/6 mice reproduces many SM features, including acute lung injury characterized by DAD, CD8+ T lymphocytes and neutrophils in the lung parenchyma, and tissular expression of proinflammatory cytokines and adhesion molecules, such as IFNγ, TNFα, ICAM, and VCAM. Since this is related to a dysregulated immune response, immunomodulatory agents are proposed to reduce the complications of SM. The monocyte locomotion inhibitory factor (MLIF) is an immunomodulatory pentapeptide isolated from axenic cultures of Entamoeba hystolitica. Thus, we evaluated if the MLIF intraperitoneal (i.p.) treatment prevented SM-induced acute lung injury. The peptide prevented SM without a parasiticidal effect, indicating that its protective effect was related to modifications in the immune response. Furthermore, peripheral CD8+ leukocytes and neutrophil proportions were higher in infected treated mice. However, the treatment prevented DAD, CD8+ cell infiltration into the pulmonary tissue and downregulated IFNγ. Moreover, VCAM-1 expression was abrogated. These results indicate that the MLIF treatment downregulated adhesion molecule expression, impeding cell migration and proinflammatory cytokine tissular production, preventing acute lung injury induced by SM. Our findings represent a potential novel strategy to avoid this complication in various events where a dysregulated immune response triggers lung injury.

Relevance of Helminth-Microbiota interplay in the host immune response.

Helminths have been present throughout the evolution of humans, promoting the development and maturation of the host immune system. However, this interaction is not exclusive between these two organisms, as the microbiota is also involved in this human evolutionary process and maintains a balanced relationship inside the host. Consequently, helminths have been forced to interact and co-evolve with the microbiota, shaping microbial communities and allowing the development of reciprocal mechanisms that favour their establishment. This helminth-microbiota association, in turn, induced the activation of different host immunoregulatory pathways to preserve health by preventing the development of some diseases associated with inflammatory immune responses. Unfortunately, this collaborative relationship can be quali- and quantitatively altered by the diet and the use of antibacterial and antihelminthic drugs. Understanding the mechanisms involved in this complex three-way communication that has continued for many years is crucial for preserving health and for the generation of new therapeutic alternatives.