Open AccessMicroRNA-155 Deficiency Exacerbates Trypanosoma cruzi Infection
Author(s) -
Bijay Kumar Jha,
Sanjay Varikuti,
Gabriella R. Seidler,
Greta Volpedo,
Abhay R. Satoskar,
Bradford S. McGwire
Publication year - 2020
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00948-19
Subject(s) - trypanosoma cruzi , biology , chagas disease , immunology , mir 155 , kinetoplastida , immune system , proinflammatory cytokine , pathogenesis , trypanosoma , innate immune system , microrna , regulator , virology , parasite hosting , inflammation , protozoal disease , gene , genetics , malaria , world wide web , computer science
Chagas disease, caused by the intracellular protozoan parasite Trypanosoma cruzi , is a public health problem affecting 6 to 8 million people, mainly in Latin America. The role of microRNAs in the pathogenesis of Chagas disease has not been well described. Here, we investigate the role of microRNA-155 (miR-155), a proinflammatory host innate immune regulator responsible for T helper type 1 and type 17 (Th1 and Th17) development and macrophage responses during T. cruzi infection. For this, we compared the survival and parasite growth and distribution in miR-155 -/- and wild-type (WT) C57BL/6 mice. The lack of miR-155 caused robust parasite infection and diminished survival of infected mice, while WT mice were resistant to infection. Immunological analysis of infected mice indicated that, in the absence of miR-155, there was decreased interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. In addition, we found that there was a significant reduction of CD8-positive (CD8 + ) T cells, natural killer (NK) cells, and NK-T cells and increased accumulation of neutrophils and inflammatory monocytes in miR-155 -/- mice. Collectively, these data indicate that miR-155 is an important immune regulatory molecule critical for the control of T. cruzi infection.