Activation/apoptosis of PMN induced by different Mtb strains prevalent in Argentina

MARÍA MERCEDES ROMERO ; LUCIANA BALBOA ; BEATRIZ LÓPEZ ; ROSA MUSELLA; LUCÍA BARRERA; EDUARDO ABBATE; MARÍA DEL CARMEN SASIAIN; MERCEDES ALEMÁN

Simposio; IV Reunión de la Sociedad Latinoamericana de Tuberculosis y otras Micobacterias (SALAMTB); 2009

Polymorphonuclear neutrophils (PMN) play a crucial role in immune response against Mtb being the first cells to arrive at sites of infection where once activated limit infection through their antimicrobial functions (phagocytosis of pathogens, degranulation, IROS generation and releasing proinflamatory cytokines). Prevalent Mtb lineages in Argentina are European-Latin American-Mediterranean (LAM) and Haarlem (H), sensible (s) as well as multi-resistance to drugs (r) strains. Objective: compare PMN response against those lineages with the reference strain H37Rv characterized to induce apoptosis associated with activation. Methods: human peripheral PMN were cultured 18 hr with or without bacteria: LAMs; Hs or Hr (M and 410 strains) thereafter their activation state measured by degranulation (CD11b and CD66b expression) and IROS production (123-DHR oxidation) as well as apoptosis (CD16 expression and PS exposure by AV binding) were measured using FACScan. Results: All LAM and Haarlem lineages induced activation with no significant differences between them in terms of CD11b and CD66b expression (p<0.05, p<0.0005 respectively). Nevertheless, despite all lineages induced IROS in absence of fMLP (p<0.05), LAM induced a higher IROS production compared to H strains (p<0.05 and stronger priming effect on PMN response to fMLP (10-6 M) (p<0.002). Consistently, strains of H lineage induced lower rates of apoptosis compared with LAM or H37Rv as assessed by AV assay (p<0.005). Conclusion: differences on activation/apoptosis seem to be ascribed to variation among Mtb lineage which may confer a characteristic innate immune response to H strains. Structural differences between strains remain to be studied.