Human naïve B cells are capable to phagocytose Mycobacterium Bovis-BCG in a lectin-assisted manner. A new innate function of adaptive lymphocytes or an immunoprivileged niche for the bug?

SCHIERLOH P; GARCÍA M; LANDONI V; KVIATCOVSKY D; BALBOA L; SASIAIN MC

Buenos Aires

Taller; I Taller sobre Evasión Inmune; 2014

Sociedad Argentina de Inmunología (SAI)/IMEX

Mycobacterium tuberculosis complex (MTC) is a genetically related group of Mycobacterium species that cause tuberculosis in humans and other mammals. These intracellular pathogens invade Professional Antigen presenting cells (APC) where they subvert the phagosome maturation in order to avoid microbicidal reactions. Herein, by in vitro infection experiments conducted under different culture conditions; we search for leukocytes other than APC that may be susceptible to M.bovis-BCG (Pasteur strain) infection. Surprisingly, human naïve B cells ?but not NK nor T cells- were able to rapidly internalize live M.bovis-BCG by a cytochalasin D-sensitive mechanism. This process was entirely dependent on the pre-coating of bacteria with tetrameric Concanavalin A (Con A) in the presence of Ca2+ (p 0.006) suggesting the involvement α-D-mannosylated glycoconjugates that are abundantly exposed over the surface of M.bovis-BCG. Given that Con A is a plant-derived lectin, we studied the effect of endogenous mannosyl-binding proteins. Interestingly, surfactant lung collectins (SP-D and SP-A) present in conditioned media and cell lysates of PMA-stimulated lung epithelial cell line (i.e A549) largely reproduce the effect of Con A (p 0.01). Similar to what recently described for Salmonella sp. in a mouse experimental setting; our results indicate that human B-cells are able to actively phagocytose lectin-opsonized-MTC. These data suggest a previously unrecognized role for adaptive lymphocytes in the context of innate resistance against tuberculosis. On the other hand, given that compared with APC, B-lymphocytes have a less developed microbicidal machinery and a more pronounced tendency to migrate, it probably constitute a more favorable niche for pathogen survival and/or tissue dissemination. All these speculations will be addressed during future experiments.