Toxoplasma gondii non-archetypal strain induces lung inflammation during acute and early chronic infection in mice.

Abstract

Toxoplasma gondii non-archetypal strains have distinct virulence profiles and immunological activation in the host when compared with archetypal strains. The present work aims to perform an analysis of the inflammatory profile during acute and early chronic infection by T. gondii atypical strain in an experimental murine model. After euthanasia, blood was collected for the quantification of specific IgG antibodies and their subtypes (IgG1/IgG3) by ELISA; bronchoalveolar lavage (BAL) was realized and immunophenotyping of lymphocytes population was performed at 12- and 30-days post infection (dpi); the levels of IFN-γ, IL-12, IL-10, TNF-α, IL-6, IL-17, nitric oxide and total proteins were determined in the BAL supernatant. Tissue cyst burden was determined in the brain homogenate, and the parasite load in the lungs was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Infection with the CK4 strain induced a lower brain cyst load similar parasite burden in the lungs, and higher levels of IgG1 and IgG3, when compared to ME49. The group infected with the CK4 strain presented higher levels of systemic IFN-γ, and both infected groups displayed similarly elevated levels of systemic TNF-α, IL-6 and IL-17 at 30 dpi, as well as higher numbers of CD4⁺ and CD8⁺ T lymphocytes in the acute stage of infection, followed by higher numbers of central and effector CD4⁺ T cells. IFN-γ levels in the BAL fluid were significantly higher in animals infected with the CK4 strain in both the acute and early chronic stage of infection, highlighting the involvement of the lung environment.