AUTHOR=Li Fei , Yu Xinxin , Li Miao , Ning Xiaoyu , Zhou Kaijian TITLE=Cryptococcal infection: host immunity, immune evasion and emerging immunotherapeutic strategies JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1671873 DOI=10.3389/fcimb.2025.1671873 ISSN=2235-2988 ABSTRACT=Cryptococcal infection is a typical opportunistic infection that significantly endangers human health, particularly to immunocompromised populations. As the top priority fungal pathogen listed by the World Health Organization, conventional antifungal drugs for cryptococcal infection are often ineffective and fail to completely eradicate the pathogen. One of the key factors underlying the treatment failure is the sophisticated immune escape strategies employed by Cryptococcus, which constitutes a major clinical challenge. Overcoming immune escape is key to improving therapeutic efficacy. Therefore, exploring new therapeutic methods, especially immunotherapy, is of paramount importance in combating the escape mechanisms and boosting the host’s defense capabilities. In this review, we focus on the host’s pattern recognition receptors, the innate and adaptive immune responses to the Cryptococcus infection, the immune escape tricks of Cryptococcus, and the prospects for immunotherapy, providing new insights for developing the anti-Cryptococcus immunotherapeutic strategies for the immunocompromised populations.