IL-1α promotes liver inflammation and necrosis during blood-stage Plasmodium chabaudi malaria

• Published in: Scientific reports 2019-05, Vol.9 (1), p.7575-7575, Article 7575
• Main Authors: de Menezes, Maria Nogueira, Salles, Érika Machado, Vieira, Flávia, Amaral, Eduardo Pinheiro, Zuzarte-Luís, Vanessa, Cassado, Alexandra, Epiphanio, Sabrina, Alvarez, José Maria, Alves-Filho, José Carlos, Mota, Maria Manuel, D’Império-Lima, Maria Regina
• Format: Article
• Language: English
• Subjects: 13/2; 13/21; 13/31; 13/51; 14/19; 14/34; 14/63; 38/90; 631/250/127/1213; 631/250/255/1629; 631/250/256; 64/60; Animals; Blood; Hepatocytes; Humanities and Social Sciences; Hypothermia; Inflammasomes; Inflammation; Inflammation - immunology; Inflammation - parasitology; Inflammation - pathology; Interleukin 1; Interleukin-1alpha - immunology; Leukocytes (neutrophilic); Liver; Liver - immunology; Liver - parasitology; Liver - pathology; Malaria; Malaria - immunology; Malaria - parasitology; Malaria - pathology; Male; Mice, Inbred C57BL; multidisciplinary; Necrosis; Parasitemia; Plasmodium chabaudi - immunology; Science; Science (multidisciplinary); Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factor-α; Vector-borne diseases
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-44125-2

Malaria causes hepatic inflammation and damage, which contribute to disease severity. The pro-inflammatory cytokine interleukin (IL)-1α is released by non-hematopoietic or hematopoietic cells during liver injury. This study established the role of IL-1α in the liver pathology caused by blood-stage P. chabaudi malaria. During acute infection, hepatic inflammation and necrosis were accompanied by NLRP3 inflammasome-independent IL-1α production. Systemically, IL-1α deficiency attenuated weight loss and hypothermia but had minor effects on parasitemia control. In the liver, the absence of IL-1α reduced the number of TUNEL + cells and necrotic lesions. This finding was associated with a lower inflammatory response, including TNF-α production. The main source of IL-1α in the liver of infected mice was inflammatory cells, particularly neutrophils. The implication of IL-1α in liver inflammation and necrosis caused by P. chabaudi infection, as well as in weight loss and hypothermia, opens up new perspectives for improving malaria outcomes by inhibiting IL-1 signaling.