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

Author(s):Show less -

de Menezes, Maria Nogueira ^[1] ; Salles, Erika Machado ^[1] ; Vieira, Flavia ^[1] ; Amaral, Eduardo Pinheiro ^[1] ; Zuzarte-Luis, Vanessa ^[2] ; Cassado, Alexandra ^[1] ; Epiphanio, Sabrina ^[3] ; Alvarez, Jose Maria ^[1] ; Alves-Filho, Jose Carlos ^[4] ; Mota, Maria Manuel ^[2] ; D'Imperio-Lima, Maria Regina ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Sao Paulo - Brazil

^[2] Univ Lisbon, Fac Med, Inst Med Mol, Lisbon - Portugal

^[3] Univ Sao Paulo, Fac Ciencias Farmaceut, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Escola Med Ribeirao Preto, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 9, MAY 20 2019.
• Web of Science Citations: 0

Abstract

Malaria causes hepatic inflammation and damage, which contribute to disease severity. The pro-inflammatory cytokine interleukin (IL)-1 alpha is released by non-hematopoietic or hematopoietic cells during liver injury. This study established the role of IL-1 alpha 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-1 alpha production. Systemically, IL-1 alpha deficiency attenuated weight loss and hypothermia but had minor effects on parasitemia control. In the liver, the absence of IL-1 alpha reduced the number ofTUNEL(+) cells and necrotic lesions. This finding was associated with a lower inflammatory response, including TNF-alpha. production. The main source of IL-1 alpha in the liver of infected mice was inflammatory cells, particularly neutrophils. The implication of IL-1 alpha 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. (AU)

• FAPESP's process: 15/20432-8 - Intervention in signaling pathways associated with the recognition of cellular damage to reduce the pathology of severe forms of malaria and tuberculosis
• Grantee: Maria Regina D'Império Lima
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/09176-4 - Role of molecules that signalize cellular damage in experimental malaria
• Grantee: Maria Nogueira de Menezes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/07140-2 - Role of inflammasomas in the pathogenesis of tuberculosis caused by hypervirulent clinical isolates of mycobacteria
• Grantee: Maria Regina D'Império Lima
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/25874-9 - Role of liver IL-1alpha in protection against superinfection during experimental malaria
• Grantee: Maria Nogueira de Menezes
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate