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Data to indicate how steroid hormones mediate the course of Neisseria gonorrhoeae disease in women are limited. Edwards (p. 1202-1213) shows that steroid hormones function together with a secreted gonococcal protein, phospholipase D, to induce cervical nitric oxide (NO) production that, in turn, promotes the intracellular survival of these bacteria. The data presented are the first to demonstrate that host-derived NO may be required to sustain cervical infection under aerobic, as well as microaerobic, conditions and that spatial differences in NO synthase expression and NO production may differentially affect bacterial cervicitis.
African trypanosomes cause serious disease in humans and livestock across large swathes of the continent. Disease outcome has been studied largely from the viewpoint of differential host responses originating from host genetic differences. Morrison et al. (p. 1096-1108) show that infections with genetically distinct trypanosome strains in one inbred strain of mouse result in distinct host pathology and gene expression patterns and that this differential pathogenesis is determined by specific pathways involved in the innate immune response. These findings suggest that parasite genetic diversity can be an important determinant of immune response polarization and disease outcome.
The inhibitory and activating forms of the paired immunoglobulin-like type 2 receptor, PILRα and PILRβ, respectively, are highly expressed on myeloid cells, but their role in immune regulation is poorly understood. Banerjee et al. (p. 1353-1363) provide the first evidence of a direct interaction between Staphylococcus aureus and PILR proteins. They show that tipping the balance in favor of inhibitory PILR signaling in mice, by activation of PILRα or deletion of PILRβ, confers resistance to acute S. aureus pneumonia. The inhibitory shift significantly alters the local and systemic cytokine milieu, which helps to control the bacterial infection and attenuate the normally overzealous inflammatory response.
Cryptococcus neoformans switches in vivo from a smooth (SM) to a hypervirulent mucoid (MC) variant. The results by Guerrero et al. (p. 1049-1057) highlight the importance of macrophages in maintaining the damage-promoting inflammation that is elicited by the hypervirulent MC variant. Alveolar macrophages isolated from both SM- and MC-infected mice are alternatively activated, but MC-infected macrophages produce more interleukin 6 (IL-6), monocyte chemoattractant protein, and arginine and differ in ligand PD-L1, ligand PD-L2, and major histocompatibility complex class II expression. The damage-promoting inflammatory response in MC-infected mice was associated with the emergence of Th17 cells and higher IL-17 lung tissue levels and was reduced by macrophage depletion.
The pili of Gram-positive bacteria are filamentous multisubunit structures covalently linked to the cell wall. Quigley et al. (p. 1294-1303) identified the residues required for covalent attachment of a model foreign protein to the pilus tip. Using this information, they expressed this hybrid pilus in the probiotic organism Lactococcus lactis. The model foreign protein retained activity, demonstrating that it is correctly folded. Furthermore, mucosal administration of this L. lactis strain to mice results in both systemic and mucosal immune responses to the foreign tip protein. This UPTOP (unhindered presentation on tips of pili) technology shows promise as a vaccine delivery system, among other possible uses.
Campylobacter causes severe enteritis in humans but colonizes the chicken gut without inducing inflammation. The basis for this difference is unknown. In this issue, de Zoete et al. (p. 1229-1238) compare activation of individual human and chicken Toll-like receptors (TLRs). Campylobacter spp. induce beta interferon production via TLR4 in human but not in chicken cells. Furthermore, Campylobacter spp. activate the chicken DNA sensor TLR21 but not human TLR9. The differential TLR recognition of Campylobacter may help to explain the different clinical manifestations between humans and chickens.
Helicobacter pylori is a major cause of upper gastrointestinal tract disease in humans. The host immune response plays a strong role in defining the outcome of H. pylori infection. Ng et al. (p. 1345-1352) demonstrate that a polymorphism within the Toll-like receptor 9 (TLR9) promoter is associated with the development of H. pylori-induced premalignant gastric changes. The presence of the variant allele creates an additional NF-κB binding site which is shown through functional analysis to induce increased ligand-dependent TLR9 transcriptional activity compared to that of the wild-type allele as a result of an increased NF-κB binding affinity for the variant promoter sequence.