Open AccessSignaling through Syk or CARD9 Mediates Species-Specific Anti-CandidaProtection in Bone Marrow Chimeric Mice
Author(s) -
Erik Zajta,
Katalin Csonka,
Anna Zsófia Tóth,
László Tiszlavicz,
Tamás Németh,
A Orosz,
Ádám Novák,
M Csíkos,
Csaba Vágvölgyi,
Attila Mócsai,
Attila Gácser
Publication year - 2021
Publication title -
mbio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.562
H-Index - 121
eISSN - 2161-2129
pISSN - 2150-7511
DOI - 10.1128/mbio.01608-21
Subject(s) - syk , candida albicans , in vivo , corpus albicans , microbiology and biotechnology , candida parapsilosis , immunity , pathogen , bone marrow , biology , fungal pathogen , signal transduction , immunology , immune system , tyrosine kinase , genetics
The spleen tyrosine kinase (Syk) and the downstream adaptor protein CARD9 are crucial signaling molecules in antimicrobial immunity. Candida parapsilosis is an emerging fungal pathogen with a high incidence in neonates, while Candida albicans is the most common agent of candidiasis. While signaling through Syk/CARD9 promotes protective host mechanisms in response to C. albicans , its function in immunity against C. parapsilosis remains unclear. Here, we generated Syk −/− and CARD9 −/− bone marrow chimeric mice to study the role of Syk/CARD9 signaling in immune responses to C. parapsilosis compared to C. albicans . We demonstrate various functions of this pathway (e.g., phagocytosis, phagosome acidification, and killing) in Candida -challenged, bone marrow-derived macrophages with differential involvement of Syk and CARD9 along with species-specific differences in cytokine production. We report that Syk −/− or CARD9 −/− chimeras rapidly display high susceptibility to C. albicans , while C. parapsilosis infection exacerbates over a prolonged period in these animals. Thus, our results establish that Syk and CARD9 contribute to systemic resistance to C. parapsilosis and C. albicans differently. Additionally, we confirm prior studies but also detail new insights into the fundamental roles of both proteins in immunity against C. albicans . Our data further suggest that Syk has a more prominent influence on anti- Candida immunity than CARD9. Therefore, this study reinforces the Syk/CARD9 pathway as a potential target for anti- Candida immune therapy.