Phagocytosis is a highly conserved, complex process that has evolved to counter the constant threat posed by pathogens, effete cells and debris. Classically defined as a mechanism for internalising and destroying particles greater than 0.5 mum in size, it is a receptor-mediated, actin-driven process. The best-studied phagocytic receptors are the opsono-receptors, FcgammaR and CR3. Phagocytic uptake involves actin dynamics including polymerisation, bundling, contraction, severing and depolymerisation of actin filaments. Recent evidence points to the importance of membrane remodelling during phagocytosis, both in terms of changes in lipid composition and delivery of new membrane to the sites of particle binding. Here we review the molecular mechanisms of phagocytic uptake and some of the strategies developed by microbial pathogens to manipulate this process.

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Pathogenic Yersinia species neutralize innate immune mechanisms by injecting type three secretion effectors into immune cells, altering cell signaling. Our study elucidates how one of these effectors, YopO, blocks phagocytosis. We demonstrate using different phagocytic models that YopO specifically blocks Rac-dependent Fc␥ receptor internalization pathway but not complement receptor 3-dependent uptake, which is controlled by Rho activity. We show that YopO prevents Rac activation but does not affect Rac accumulation at the phagocytic cup. In addition, we show that plasma membrane localization and the guanine-nucleotide dissociation inhibitor (GDI)-like domain of YopO cooperate for maximal anti-phagocytosis. Although YopO has the same affinity for Rac1, Rac2, and RhoA in vitro, it selectively interacts with Rac isoforms in cells. This is due to the differential localization of the Rho family G proteins in resting cells; Rac isoforms partially exist as a GDI-free pool at the membrane of resting cells, whereas RhoA is trapped in the cytosol by RhoGDI␣. We propose that YopO exploits this basic difference in localization and availability to selectively inhibit Rac-dependent phagocytosis.

Parenteral MenB vaccination selectively reprograms preexisting naturally acquired mucosal immunity. As new-generation protein-based MenB vaccine candidates undergo evaluation, the impact of these vaccines on mucosal immunity in both adults and children will need to be addressed.

T cell memory to human papillomavirus can be identified in tonsil tissue from an adult population in the absence of concurrent HPV infection. How novel HPV vaccines might augment this preexisting cell-mediated immunity is an essential area for investigation.

Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are associated with increased sensitivity to tyrosine kinase inhibitors (TKIs) and are present in 10% to 30% of nonsmall cell lung carcinoma depending on ethnic origin. EGFR protein is also overexpressed in about 90% of squamous cell carcinoma of head and neck (HNSCC), and treatment with TKIs has shown clinical benefit in a subgroup of these patients. Recently, EGFR mutations were described in three Asian patients with larynx cancer. METHODS: The presenters screened for EGFR tyrosine kinase mutations in tumor DNA of 100 patients of Caucasian origin with HNSCC by direct sequencing of the hotspot regions. Two patients displayed a novel, somatic EGFR missense mutation, K745R, affecting a highly conserved residue within the ATP cleft.