FN-gamma Mediated Signaling Improves Fungal Clearance in Experimental Pulmonary Mucormycosi

Author(s):Show less -

Dos Santos, Amanda Ribeiro ^{[1, 2]} ; Fraga-Silva, Thais Fernanda ^[3] ; Almeida-Donanzam, Debora De Fatima ^{[1, 2]} ; Dos Santos, Rodolfo Ferreira ^[1] ; Finato, Angela Carolina ^[1] ; Soares, Cleverson Teixeira ^[4] ; Lara, Vanessa Soares ^[5] ; Martins Almeida, Nara Ligia ^[5] ; Andrade, Maria Izilda ^[4] ; de Arruda, Olavo Speranza ^[1] ; Parreira de Arruda, Maria Sueli ^[1] ; Venturini, James ^{[1, 2]}

Affiliation

^[1] Univ Estadual Paulista, Fac Ciencias, UNESP, BR-17033360 Bauru, SP - Brazil

^[2] Univ Fed Mato Grosso Sul UFMS, Fac Med, Unit 9, BR-79070900 Campo Grande, MS - Brazil

^[3] Univ Sao Paulo, Dept Bioquim & Imunol, Escola Med Ribeirao Preto, BR-14049900 Sao Paulo, SP - Brazil

^[4] Lauro de Souza Lima Inst, BR-17034971 Bauru, SP - Brazil

^[5] Univ Sao Paulo, Fac Odontol Bauru FOB, BR-17012901 Bauru, SP - Brazil

• Document type: Journal article
• Source: Mycopathologia; v. 187, n. 1 OCT 2021.
• Web of Science Citations: 2

Abstract

We established three immunocompetent murine models of pulmonary mucormycosis to determine the involvement of the adaptive immune response in host resistance in pulmonary mucormycosis, a rapidly fatal disease caused mainly by Rhizopus spp. Immunocompetent inbred (C57BL/6, BALB/c) and outbred (Swiss) strains of mice were inoculated with R. oryzae via the intratracheal route. The inoculation resulted in a disseminated infection that spread to the brain, spleen, kidney, and liver. After 7 and 30 days of R. oryzae infection, BALB/c mice showed the lowest fungal load and highest production of IFN-gamma and IL-2 by splenocytes. Swiss mice showed a higher fungal load 30 days p.i. and was associated with a weak development of the Th-1 profile. To confirm our findings, R. oryzae-infected IFN-gamma(-)/(-) mice were evaluated after 60 days, where the mice still showed viable fungi in the lungs. This study showed, for the first time, that pulmonary mucormycosis in three widely used mouse strains resulted in an acute fungal dissemination without immunosuppression whose outcome varies according to the genetic background of the mice. We also identified the partial role of IFN-gamma in the efficient elimination of R. oryzae during pulmonary infection. (AU)

• FAPESP's process: 13/15513-3 - Contribution to the study of mucormycosis: development of an experimental murine model
• Grantee: Amanda Ribeiro dos Santos
• Support Opportunities: Scholarships in Brazil - Scientific Initiation