Boosting innate immunity: Asaia bacteria expressing a protein from Wolbachia determine macrophage activation and killing of Leishmania parasites

Leishmaniases are severe vector-borne diseases affecting humans and animals, caused by Leishmania protozoans. Immune polarization is thought to play a major role in determining the outcome of most Leishmania infections: hosts displaying M1-polarized macrophages are protected, while those biased on the M2 side acquire a chronic infection, eventually developing into an overt and potentially deadly disease. The identification of the factors involved in M1 polarization is essential for the design of therapeutic and prophylactic interventions, including vaccines. Several lines of evidence suggest that infection by the filarial nematode Dirofilaria immitis is one of the factors that interfere with leishmaniasis in dogs. Indeed, filarial nematodes induce a partial skew of the immune response towards M1, likely caused by their bacterial endosymbionts, Wolbachia. Here we have examined the potential of AsaiaWSP, a bacterium engineered for the expression of the Wolbachia surface protein (WSP), as an inductor of M1 macrophage activation and Leishmania killing. Macrophages stimulated with AsaiaWSP displayed a strong leishmanicidal activity, that was comparable to that determined by the choice-drug amphotericin B. Additionally, AsaiaWSP determined the expression of markers of classical macrophage activation, including M1 cytokines, ROS and NO, and an increase in phagocytosis activity. Asaia not expressing WSP also determined an activation of macrophages, although at a slightly lower extent compared to AsaiaWSP. In summary, our study, while providing a strong evidence for the immune-stimulating properties of the Wolbachia surface protein, highlights the potential of Asaia, either native or engineered as AsaiaWSP, as an immunomodulating agent, worth of further investigations in the areas of immune-prophylaxis and therapy, of leishmaniases and other pathologies.