CyaA delivered by B. pertussis OMVs dampens human neutrophils protective function

ALVARES HAYES JIMENA; BLANCÁ, BRUNO; VALDEZ, HUGO; DEBANDI, MARTINA; LAMBERTI, YANINA; RODRIGUEZ, MARIA EUGENIA

Vancouver

Simposio; 13th International Bordetella Symposium; 2022

International Society of Bordetella

Outer membrane vesicles (OMVs) secreted by pathogenic bacteria are usually loaded with virulence factors that are delivered to the host cells during infection, eventually compromising the host defense response. We recently observed that B. pertussis (Bp) OMVs shape the interaction of this pathogen with macrophages favoring bacterial persistence. We here evaluated the influence of OMVs on the interaction of Bp with polymorphonuclear leukocytes (PMN), the other sentinel cells involved in host defense against invading pathogens. We found that OMVs internalization by PMN led to a decrease in the expression of cell surface CR3 and FcγR, which proved to be dependent on the adenylate cylase toxin (CyaA) delivered by these vesicles. The decrease in CR3 and FcγR expression determined a drop in the PMN uptake of bacteria in the absence or the presence of antibodies, respectively. CyaA delivered by OMVs further proved to modulate the cellular response to the bacterial interaction through either CR3 or FcgR, determining a decrease in the bacterial trafficking to lysosomes, as assessed by bacterial colocalization with the lysosomal markers, and a concomitant increase in the bacterial intracellular survival. On the other hand, if both OMVs and Bp were incubated with anti-Bp sera containing anti-CyaA antibodies, the presence of these vesicles did not affect the intracellular bactericidal trafficking but led to a significant decrease of the PMN bacterial uptake due to the competition for FcγR on PMN. Altogether, these results suggest a relevant role of Bp OMVs in the bacterial survival both in naïve and immune hosts.