Clinical isolates of Mycobacterium tuberculosis in Argentina differentially induces respiratory burst via TLR2 and dectin-1 in neutrophils as possible mechanism of immune escape

M. ROMERO, J. I. BASILE, B. LOPEZ, V. RITACCO, L. BARRERA, M. C. SASIAIN, M. ALEMAN

Milan

Congreso; 15th International Congress of Immunology; 2013

IUIS

Some years ago it was thought that both illness and latency of Tuberculosis (TB) were primary related by host factors. Nonetheless, it becomes evident that there are also factors from the bacteria which participate. The goal of this study was to characterize the immune response of multidrug-resistant clinical isolates representative of the most successful families in South America (LAM and Haarlem). We observed that Ra from LAM family, induce high levels of apoptosis, dependent on ROS generation and mediated by dectin-1 and TLR2, with subsequent activation of the Syk and p38 pathways. In this process, lipid rafts coalescence is a key step for assembly of the NADPH oxidase. We propose the α-glucan of the mycobacterial capsule as potential ligands Mtb dectin-1, triggering ROS generation, via Syk activation in PMN. Particularly, the clinical isolate M, does not induce apoptosis as a result of poor induction of ROS, associated with a deficient lipid rafts formation and no or faulty interaction with dectin-1. These observed differences among clinical isolates of Mtb may be associated with structural and / or spatial variations of the cell wall, which condition their interaction with the target cell. Thus, we postulate that differences in composition of the cell wall at the level of α-glucans and ligands for TLR2, allow some bacteria to hide from the immune system, acting as a potential evasion mechanism, permitting perpetuation