Search

Co‐evolutionary adaptation of hookworms with their mammalian hosts has been selected for immunoregulatory excretory/secretory (E/S) products. However, it is not known whether, or if so, how host immunological status impacts the secreted profile of hematophagous adult worms. This study interrogated the impact of host Signal transducer and activator of transcription 6 (STAT6) expression during the experimental evolution of hookworms through the sequential passage of the life cycle in either STAT6 deficient or WT C57BL/6 mice. Proteomic analysis of E/S products by LC–MS showed increased abundance of 15 proteins, including myosin‐3, related to muscle function, and aconitate hydratase, related to iron homeostasis. However, most E/S proteins (174 of 337 unique identities) were decreased, including those in the Ancylostoma‐secreted protein (ASP) category, and metallopeptidases. Several identified proteins are established immune‐modulators such as fatty acid‐binding protein homologue, cystatin, and acetylcholinesterase. Enrichment analysis of InterPro functional categories showed down‐regulation of Cysteine‐rich secretory proteins, Antigen 5, and Pathogenesis‐related 1 proteins (CAP), Astacin‐like metallopeptidase, Glycoside hydrolase, and Transthyretin‐like protein groups in STAT6 KO‐adapted worms. Taken together, these data indicate that in an environment lacking Type 2 immunity, hookworms alter their secretome by reducing immune evasion proteins‐ and increasing locomotor‐ and feeding‐associated proteins. [ABSTRACT FROM AUTHOR]

Myeloid phagocytes are essential for antifungal immunity against pulmonary Aspergillus fumigatus and systemic Candida albicans infections. However, the molecular mechanisms underlying fungal clearance by phagocytes remain incompletely understood. In this study, we investigated the role of perforin-2 ( Mpeg1 ) in antifungal immunity. We found that Mpeg1 -/- mice generated on a mixed C57BL/6J-DBA/2 background exhibited enhanced survival, reduced lung fungal burden, and greater neutrophil fungal killing activity compared to wild-type C57BL/6J (B6) mice, suggesting that perforin-2 may impair antifungal immune responses. However, when we compared Mpeg1 -/- mice with co-housed Mpeg +/+ littermate controls, these differences were no longer observed, indicating that initial findings were likely influenced by differences in the murine genetic background or the microbiota composition. Furthermore, perforin-2 was dispensable for antifungal immunity during C. albicans bloodstream infection. These results suggest that perforin-2 is not essential for host defense against fungal infections in otherwise immune competent mice and highlight the importance of generating co-housed littermate controls to minimize murine genetic and microbiota-related factors in studies of host defense mechanisms.