ROLE OF RAB 14 DURING PHAGOSOMAL MATURATION AND ITS IMPLICATION IN THE DROSOPHILA MELANOGASTER IMMUNE RESPONSE

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2012

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Phagocytosis is a vital component of Drosophila cellular immunity. The sequential interaction of a phagosome with the endocytic compartments entails docking and fusion and requires the role of many RabGTPases. We identified Rab14 as a possible regulator of phagosome maturation in an in vivo screen. Expression studies indicated the presence of Rab14 in hemocytes in both larval and adult stages. To further characterize the role of Rab14 during phagocytosis, a Rab14null mutant was generated. The Rab14 mutant displayed no difference in the phagocytic uptake of E.coli or S.aureus, however the kinetics of phagosome maturation for both microbes was decreased. Cell biology studies indicated delayed acquisition of the late endosomal marker, Rab7 and the lysosomal marker, Spinster, on the S.aureus phagosome. Since recruitment of the early endosomal marker Rab5 was not affected, we concluded Rab14 functions downstream to Rab5 and is essential for efficient Rab7 recruitment on microbial phagosomes. Rab14 itself was recruited during both the early and late phagosomal stages and in accordance with that, it showed colocalization with both Rab5 and Rab7 on endosomes. Rab14 mutants also showed a defect in endosomal maturation, suggesting Rab14 is also essential during endocytosis. Rab14 mutants demonstrated defects in the induction of the specific antimicrobial peptides Cecropin and Defensin in response to S.aureus infection, indicating a possible crosstalk between the cellular and humoral response. Along with that, Rab14 mutants also showed defects in the expression of the Toll ligand Spatzle, in response to infection. Hence we propose Rab14 regulates expression of specific antimicrobial peptides through the cytokine Spatzle. The inefficient cellular and humoral responses result in increased susceptibility of Rab14 mutants to bacterial infection. This could be rescued by hemocyte-specific expression of Rab14, suggesting its role in the hemocytes is essential for the immune response against S. aureus. Our study identifying a role for Rab14 during phagosomal maturation gives insight on the pathogenesis of M.tuberculosis, a pathogen which manipulates Rab14 to subvert phagosome maturation. Moreover it identifies Rab14 function during cellular and humoral responses as an integral component of the Drosophila immune response against S.aureus.

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