Dectin-3 Is Not Required for Protection against Cryptococcus neoformans Infection

TLDR

C‑type lectin receptors are pattern‑recognition proteins that orchestrate immune responses to pathogens, and Dectin‑3, a myeloid‑cell CLR, binds mycobacterial trehalose dimycolate and fungal α‑mannans. The study aimed to determine whether Dectin‑3 contributes to protective immunity against *Cryptococcus neoformans*. Using a murine model of pulmonary cryptococcosis, the authors compared Dectin‑3‑deficient mice to wild‑type controls to assess immune responses. Dectin‑3 deficiency did not increase susceptibility, alter leukocyte recruitment, cytokine production, or phagocytic/anti‑cryptococcal activity, indicating that Dectin‑3 is dispensable for protection against pulmonary *C.

Abstract

C-type lectin receptors (CLRs) are diverse, trans-membrane proteins that function as pattern recognition receptors (PRRs) which are necessary for orchestrating immune responses against pathogens. CLRs have been shown to play a major role in recognition and protection against fungal pathogens. Dectin-3 (also known as MCL, Clecsf8, or Clec4d) is a myeloid cell-specific CLR that recognizes mycobacterial trehalose 6,6'-dimycolate (TDM) as well as α-mannans present in the cell wall of fungal pathogens. To date, a potential role for Dectin-3 in the mediation of protective immune responses against C. neoformans has yet to be determined. Consequently, we evaluated the impact of Dectin-3 deficiency on the development of protective immune responses against C. neoformans using an experimental murine model of pulmonary cryptococcosis. Dectin-3 deficiency did not lead to increased susceptibility of mice to experimental pulmonary C. neoformans infection. Also, no significant differences in pulmonary leukocyte recruitment and cytokine production were observed in Dectin-3 deficient mice compared to wild type infected mice. In addition, we observed no differences in uptake and anti-cryptococcal activity of Dectin-3 deficient dendritic cells and macrophages. Altogether, our studies show that Dectin-3 is dispensable for mediating protective immune responses against pulmonary C. neoformans infection.