Innate reproductive immunity: How does a reproductive organ distinguish sperm from microbes in bedbugs?

• Applicant: Professor Dr. Klaus Reinhardt
• Subject Area: Animal Physiology and Biochemistry
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 527520243

Immunity, an organism's ability to defend itself against pathogens and damaged tissue, has two major arms, the innate and the adaptive immune system. Non-vertebrate organisms rely on the former and recognise pathogens mainly by conserved pattern recognition receptors. How the innate immune system interacts with the reproductive system (reproductive immunology) is largely neglected, especially for invertebrates. One of the most exciting research questions in innate reproductive immunology is how the allegedly unspecific innate immune system distinguishes detrimental non-self cells, such as pathogens, from beneficial non-self cells such as gametes. The present proposal will address this question using a novel model species, the common bedbug Cimex lectularius, where an organ secondarily evolved – the spermalege (SL) – that functions in reproductive immunity. Here we address the following key questions of innate reproductive immunology: i) Which key players – cells, receptors, and effectors – are involved in reproductive immunity? ii) Are these key players distinct from those involved in systemic immunity? iii) Does microbe recognition and clearance by the female reproductive immune system work differently than the systemic immune system? iv) How are recognition and selective clearance of sperm mediated? Bedbugs are an exceptionally practical system of reproductive immunology: the male injects sperm straight into the female body cavity with a penetration device, bypassing the regular female reproductive tract by traumatic insemination (TI). Since TI-associated wounding accompanies a high risk of microbe transmission, bedbug females have evolved a unique paragenital organ, the mesospermalege (MSL). MSL cells recognise and remove sexually transmitted microbes but can also phagocytise sperm and seminal fluid. Our preliminary work has established that the MSL contains morphologically different phagocytes capable of clearing microbes and sperm, and that target-specific phagocytosis receptors are expressed by subsets of these cells. Based on these findings we test the following predictions: i) the population of phagocytic immune cells of the MSL is unique in composition and function. ii) the phagocytosis of the MSL immune cells is specific and differentiates between sexually transmitted microbes and sperm. iii) this differential response is based on specific phagocytosis receptors. iv) the regenerative process producing these immune cells in the MSL is similar to haematopoiesis. Understanding the cellular immune response including the involved pattern recognition in a reproduction-associated immune organ will enable us to understand the specificity of the innate reproductive immune system.

• DFG Programme: Research Grants