Endosymbiotic RNA virus inhibits Leishmania-induced caspase-11 activation

Author(s)

de Carvalho, Renan V. H. ^{[1, 2]} ; Lima-Junior, Djalma S. ^{[3, 1]} ; de Oliveira, V, Caroline ; Zamboni, Dario S. ^[4]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, FMRP USP, Fac Med Ribeirao Preto, Dept Biol Celular & Mol &, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Rockefeller Univ, Lab Lymphocyte Dynam, 1230 York Av, New York, NY 10065 - USA

^[3] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 - USA

^[4] de Oliveira, Caroline, V, Univ Sao Paulo, Ribeirao Preto Med Sch, FMRP USP, Fac Med Ribeirao Preto, Dept Biol Celular & Mol &, Av Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: ISCIENCE; v. 24, n. 1 JAN 22 2021.
• Web of Science Citations: 0

Abstract

New World species of the intracellular protozoan parasites of the Leishmania genus can cause mucocutaneous leishmaniases. The presence of an endosymbiotic Leishmania RNA virus (LRV) in Leishmania guyanensis (L.g.) promotes disease exacerbation and the development of mucocutaneous disease. It was previously reported that LRV blocks the NLRP3 inflammasome, but additional mechanisms remain unclear. Here, we investigated whether LRV interferes with the inflammasome via caspase-11, which induces non-canonical NLRP3 activation and was reported to be activated by Leishmania. By using macrophages and mice, we found that LRV inhibits caspase-11 activation and IL-1 beta release by L.g. in a TLR3- and ATG5-dependent manner. Moreover, LRV exacerbates disease in C57BL/6 mice but not in Casp11(-/-), Nlrp3(-/-), and 129 mice, a mouse strain that is naturally mutant for caspase-11. These results demonstrate that LRV interferes with caspase-11 activation by Leishmania, expanding our understanding about the mechanisms by which LRV promotes disease exacerbation. (AU)

• FAPESP's process: 19/11342-6 - Mechanisms and consequences of the activation of cytoplasmic receptors by intracellular pathogens
• Grantee: Dario Simões Zamboni
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 18/14398-0 - UK:Brazil Joint Centre Partnership in Leishmaniasis (JCPiL)
• Grantee: Angela Kaysel Cruz
• Support Opportunities: Research Projects - Thematic Grants