Epithelial cells can respond to conserved bacterial products that are internalized after either bacterial invasion or liposome treatment of cells. We report here that the noninvasive Gram-negative pathogen Helicobacter pylori was recognized by epithelial cells via Nod1, an intracellular pathogen-recognition molecule with specificity for Gram-negative peptidoglycan. Nod1 detection of H. pylori depended on the delivery of peptidoglycan to host cells by a bacterial type IV secretion system, encoded by the H. pylori cag pathogenicity island. Consistent with involvement of Nod1 in host defense, Nod1-deficient mice were more susceptible to infection by cag pathogenicity island-positive H. pylori than were wild-type mice. We propose that sensing of H. pylori by Nod1 represents a model for host recognition of noninvasive pathogens.

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Influenza A virus (IAV) infection results in a highly contagious respiratory illness leading to substantial morbidity and occasionally death. In this report, we assessed the in vivo physiological contribution of invariant NKT (iNKT) lymphocytes, a subset of lipid-reactive αβ T lymphocytes, on the host response and viral pathogenesis using a virulent, mouse-adapted, IAV H3N2 strain. Upon infection with a lethal dose of IAV, iNKT cells become activated in the lungs and bronchoalveolar space to become rapidly anergic to further restimulation. Relative to wild-type animals, C57BL/6 mice deficient in iNKT cells (Jα18−/− mice) developed a more severe bronchopneumonia and had an accelerated fatal outcome, a phenomenon reversed by the adoptive transfer of NKT cells prior to infection. The enhanced pathology in Jα18−/− animals was not associated with either reduced or delayed viral clearance in the lungs or with a defective local NK cell response. In marked contrast, Jα18−/− mice displayed a dramatically reduced IAV-specific CD8+ T cell response in the lungs and in lung-draining mediastinal lymph nodes. We further show that this defective CD8+ T cell response correlates with an altered accumulation and maturation of pulmonary CD103+, but not CD11bhigh, dendritic cells in the mediastinal lymph nodes. Taken together, these findings point to a role for iNKT cells in the control of pneumonia as well as in the development of the CD8+ T cell response during the early stage of acute IAV H3N2 infection.

The molecular epidemiology of Helicobacter pylori in Africa is poorly documented. From January 2007 to December 2008, we investigated 187 patients with gastric symptoms in one of the main tertiary hospitals in Dakar, Senegal. One hundred and seventeen patients were culture-positive for H. pylori. Polymorphisms in vacA and cagA status were investigated by PCR; the 3'-region of cagA was sequenced, and EPIYA motifs were identified. Bacterial heterogeneity within individuals was extensively assessed by using an approach based on vacA and cagA heterogeneity. Fourteen per cent of H. pylori-positive patients displayed evidence of mixed infection, which may affect disease outcome. Patients with multiple vacA alleles were excluded from subsequent analyses. Among the final study population of 105 patients, 29 had gastritis only, 61 had ulcerated lesions, and 15 had suspicion of neoplasia based on endoscopic findings. All cases of suspected neoplasia were histologically confirmed as gastric cancer (GC). The cagA gene was present in 73.3% of isolates. CagA proteins contained zero (3.7%), one (93.9%) or two (2.4%) EPIYA-C segments, and all were western CagA. Most of the isolates possessed presumed high-vacuolization isotypes (s1i1m1 (57.1%) or s1i1m2 (21.9%)). Despite the small number of cases, GC was associated with cagA (p 0.03), two EPIYA-C segments in the C-terminal region of CagA (p 0.03), and the s1 vacA allele (p 0.002). Multiple EPIYA-C segments were less frequent than reported in other countries, possibly contributing to the low incidence of GC in Senegal.