Surfactant protein D regulates murine testicular immune milieu and sperm functions

Problem: Surfactant protein D (SP-D), a pattern recognition protein that regulates inflammation and immune homoeostasis, is expressed by testicular germ cells under the influence of testosterone. This study investigates the role of SP-D in testicular immune privilege and sperm functions. Method of study: Testicular levels of cytokines and immunoregulatory molecules were evaluated in lipopolysaccharide (LPS)-challenged SP-D gene knockout mice (SP-D^−/−). Further, sperm functions were assessed by computer-assisted sperm analyser (CASA) and in vitro capacitation. The effect of a recombinant fragment of human SP-D (rhSP-D) on LPS-induced testicular inflammation and sperm motility was assessed in wild-type (WT) mice. Result: Endogenous absence of SP-D led to significantly increased testicular levels of immunosuppressive molecules, viz. serpina3, TGF-β1 and IL-10, and reduced levels of immune cell activation markers, CD86, IL-2 and ITGAX. These compensatory mechanisms resulted in markedly blunted levels of TNF-α, IL-12p40, MIP-1α, G-CSF and IL-6 in response to LPS challenge. Notably, exogenous supplementation of rhSP-D salvaged the WT mice from LPS-induced pro-inflammatory immune response and impairment of sperm motility by upregulating the levels of TGF-β1 and IL-10. Conclusion: The study highlights the involvement of SP-D in maintenance of testicular immune privilege and its indirect contribution to male fertility.