Human Leukocyte Antigen-G is enriched in presence of trypanosome in the dermis of individuals exposed to gambiense Human African Trypanosomiasis in Guinea and Côte d’Ivoire

Human leukocyte antigen-G (HLA-G) is an immunomodulatory molecule known to play a crucial role in immune tolerance and regulation. In the context of human African trypanosomiasis (HAT), higher soluble HLA-G levels were detected in the plasma of confirmed cases, representing a serological marker of T. b. gambiense infection. As trypanosomes also invade extravascular tissues, especially the skin, this study explored the potential role of HLA-G in the dermal immune response during T. b. gambiense infection. Blood and skin samples from 50 seronegative individuals, 45 seropositive suspects and 36 confirmed HAT cases, collected between 2018 and 2022 in endemic foci of Guinea and Côte d'Ivoire, were analyzed. Plasmatic and dermal levels of HLA-G proteins were quantified by ELISA and immuno-histochemistry, respectively, and compared to the trypanosome detection results in the same samples. The implication of soluble HLA-G plasma level as a biomarker of T. b. gambiense infection was confirmed. In the dermis, HLA-G isoforms were expressed either with a granular distribution or with in diffuse halos. Granular patterns of dermal HLA-G were directly associated with the presence of trypanosomes in the dermis. The presence of diffuse halos was correlated to higher sHLA-G levels in the plasma. In total, this study provides the first evidence of the involvement of HLA-G in the extravascular immune response against parasites, especially in the skin. It shows that HLA-G distribution in the extravascular compartment also represents a biomarker of trypanosome infection.