The Effect of CD300A Receptor on Caspase-1 Activity in the Context of Cell Death and on Its Activators Nlrp3 and Asc in Sertoli Cells

Abstract

The phagocytosis of spermatozoa cytoplasm by Sertoli cells is a key maturation event during spermiation and takes place in a blood-testis barrier maintained immune-privileged environment that is essential for the prevention of the sperm self-antigens from presentation. We have recently discovered Nlrp3 inflammasome to be functional in Sertoli cells upon TLR4 and NOD receptors challenge in ATP danger presence, resulting in release of pro-inflammatory cytokines and cell death that could potentially result in breaking of the selftolerance. In this context we have investigated, the considered inhibitory, phagocytic receptor CD300a that is able to detect eventually sperm cell surface apoptotic signals. We found CD300a to be essential for Nlrp3 inflammasome activation via CD300a-dependent Asc expression and both caspase-1 and caspase-3 activation, since its gene silencing abrogated these events. At the same time CD300a demonstrated bi-directional regulatory abilities, supressing Gasdermin D inflammasome effector pro- and activated forms. CD300a had a restrictive effect on cell population level reducing caspase positive cells in strong caspase-1 and 3, and weak caspase-3 expressing dead cells, suggesting key regulatory role in Sertoli cell faith. CD300a should be further explored as its potential perturbation could play a role in putative self-antigen-tolerance
perturbation and thus contribute to male infertility.