|Home | About | Journals | Submit | Contact Us | Français|
Synthesis of trehalose by pathogenic yeast such as Candida albicans and Cryptococcus neoformans confers resistance to a variety of environmental stresses and is required for full virulence. Al-Bader et al. (p. 3007-3018) demonstrate that trehalose synthesis by the mold Aspergillus fumigatus, while conferring resistance to stress, actually suppresses virulence. This phenotype is linked to alterations in the fungal cell wall that lead to enhanced macrophage phagocytosis. In addition to linking trehalose metabolism to cell wall polysaccharide synthesis, these findings suggest that inhibition of trehalose synthesis is unlikely to be an effective antifungal strategy because it increases A. fumigatus virulence.
Dendritic cells (DC) are critical for eliciting a strong protective CD8+ T-cell response against Encephalitozoon cuniculi. Lawlor et al. (p. 3097-3102) report that priming of this T-cell subset is strongly dependent on upregulation of the Toll-like receptor 4 (TLR4) molecule by DC. Blockade of TLR4 prior to E. cuniculi stimulation of DC severely reduces the ability to elicit a robust CD8+ T-cell response both in vitro and in vivo. Thus, optimal CD8+ T-cell induction against E. cuniculi is strongly dependent on TLR4-mediated signaling, and its absence may severely compromise the host's ability to control the pathogen.
Helminth infections have been associated with protection against inflammatory diseases. Figueiredo et al. (p. 3160-3167) demonstrate that chronic infections with Ascaris lumbricoides and Trichuris trichiura are associated with elevated spontaneous interleukin-10 and reduced Th1 and Th2 cytokine responses to mitogen, indicating that chronic infections are associated with immune hyporesponsiveness.
Pseudomonas aeruginosa is a motile opportunistic pathogen which commonly infects the lungs of cystic fibrosis (CF) patients. Establishment within the CF lung correlates with the downregulation of flagellar gene expression; however, it is unclear why the loss of the flagellum enables evasion of the innate immune response. Using in vitro and in vivo techniques, Amiel et al. (p. 2937-2945) demonstrate that it is the loss of flagellum-based motility, rather than the loss of the flagellum itself, which confers resistance to phagocytosis. These findings provide insights into how the loss of motility affords an advantage to P. aeruginosa with regard to phagocytic clearance.
Infection with Campylobacter jejuni can lead to the development of Guillain-Barré syndrome (GBS), an antibody-mediated autoimmune disease affecting the peripheral nerves. Expression of specific sialylated glycolipids on the surface of the bacterial cell is the main known pathogenic factor for development of the disease. Heikema et al. (p. 3237-3246) demonstrate that the sialylated glycolipids are able to bind to sialoadhesin, a sialic acid binding Ig-like lectin expressed on a subset of macrophages, which has been linked to various other autoimmune diseases. These findings provide new insights into host-pathogen interactions that might be involved in the development of GBS.
Pertactin (PRN) is a highly immunogenic surface-localized autotransporter protein produced by Bordetella pertussis, B. parapertussis, and B. bronchiseptica. It is commonly referred to as an adhesin with a functionally important Arg-Gly-Asp (RGD) triplet. Inatsuka et al. (p. 2901-2909), however, found no evidence of adhesive activity for PRN in B. bronchiseptica. Instead, they found that PRN, but not its RGD motif, is required for growth of B. bronchiseptica in the lower respiratory tract, and experiments with immunodeficient and neutropenic mice revealed an important role for PRN in resisting neutrophil-mediated clearance.
Complement receptor 1 (CR1) has long been known to contribute to the clearance of complement-containing immune complexes from blood. The mechanism appears to be the binding of C3b-containing immune complexes to CR1 on erythrocytes, which then transfer the complexes to phagocytes. It has been suspected that CR1 similarly plays a role in the clearance of opsonized bacteria. Li et al. (p. 3129-3135) used transgenic mouse erythrocytes expressing human CR1 to show that an interaction between CR1 and the C3 deposited on pneumococci leads to accelerated clearance of pneumococci from the blood of mice. Since mouse erythrocytes lack CR1, these data indicate that pneumococcal studies with conventional mice might underestimate the protective efficacy of complement-fixing antibodies in man.