This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content

Next Article 

Infection and Immunity, June 2008, p. 2257-2258, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.00473-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

SPOTLIGHT

Articles of Significant Interest Selected from This Issue by the Editors

Chlamydia trachomatis secretes proteins to the membrane that separates the chlamydial organisms from the rest of host cell cytosol. These proteins are called inclusion membrane proteins, or Incs, and they are thought to mediate chlamydial interactions with host cells. The first step for learning how the Incs work is to identify them. Using an anti-fusion protein antibody approach, Li et al. (p. 2746-2757) screened 50 putative Inc proteins for their locations in Chlamydia-infected cells. They identified four new Incs, which brings the total number of experimentally demonstrated Incs to 22 for C. trachomatis. Interestingly, the inclusion membrane-localized proteins were more dominantly recognized than other chlamydial proteins localized elsewhere by antisera from women urogenitally infected with C. trachomatis, and the immunodominance was mapped to the regions predicted to be exposed on the host cell cytoplasmic side of the inclusion membrane. It will be worth testing whether the immunodominance of Incs can lead to protective immunity against chlamydial infection or whether it represents a chlamydial decoy for directing the infected host to mount unproductive immune responses.

Antibody Independent Protection against Pneumoccoccal Carriage Is Antigen Specific

CD4⁺ T-cell-mediated, antibody-independent immunity plays a critical role in the protection against Streptococus pneumoniae carriage. Using mice that lack mature B and T cells except for CD4⁺ T cells specific for the ovalbumin (OVA) peptide and pneumococcal strains modified to express OVA, Trzciski et al. (p. 2678-2684) demonstrate that this immunity is induced in an antigen-specific fashion and requires specific antigen for recall responses. However, effector action is not limited to antigen-expressing bacteria, an observation consistent with recruitment of nonspecific effectors by antigen-specific CD4⁺ T cells. These results are relevant to the development of new vaccine strategies.

Nitric Oxide Mediates Suppression of Cellular Immune Responses in Hookworm Infection

Hookworms, which infect nearly one billion people, impair host cellular immune responses, thereby altering the course of infection with the parasite as well as with other pathogens. Dondji et al. (p. 2560-2567) demonstrate that nitric oxide secreted by splenocytes from infected animals mediates suppression of lymphocyte proliferation. In addition, they show that infection is associated with impaired antigen presentation and CD4⁺ T-cell depletion, thus defining three potential mechanisms by which intestinal nematodes suppress host immunity. This work confirms limited data from populations in areas where nematode infections are prevalent and further validates the use of a permissive animal host model for the study of human disease.

Genes That Are Particularly Sensitive to Lipopolysaccharide in Human Monocytes

The role of lipopolysaccharide (LPS) has been more accurately defined in meningococcal infections than in other gram-negative infections. In a detailed gene expression study of human monocytes, Øvstebø et al. (p. 2685-2695) have identified 2,288 genes to be particularly sensitive to LPS by comparing the effects of wild-type and LPS-deficient Neisseria meningitidis strains. LPS operates through the Toll-like receptor pathways where, in addition to the MyD88-dependent pathway, LPS was shown to be a prerequisite for the MyD88-independent pathway, leading to beta interferon (IFN-β) transcription and synthesis of IFN-β-inducible genes, such as CXCL10 mRNA. This LPS-induced chemokine production in vitro was further substantiated to occur in vivo as documented by increased levels of CXCL10 in plasma specimens from patients with meningococcal infection and high levels of LPS (fulminant septicemia) compared with plasma specimens containing low levels of LPS (meningitis).

Moraxella catarrhalis Expresses an Unusually Large Hfq Protein

The Sm-like protein Hfq is a posttranscriptional regulator that can bind small RNA molecules. Attia et al. (p. 2520-2530) characterize this macromolecule in the mucosal pathogen Moraxella catarrhalis, showing that it is at least twice as large as other Hfq proteins characterized to date. Additionally, an M. catarrhalis hfq mutant displayed a novel phenotype that has not been reported previously for hfq mutants. The M. catarrhalis hfq mutant grew better than its wild-type parent strain in a continuous flow biofilm system, raising the possibility that one or more key elements in biofilm development by this pathogen may involve regulation by small RNA molecules.

Type IV Pilus-Mediated Infection: Is It Necessarily Bad for the Host?

Many microbes that associate with their host for extended periods dampen apoptotic signaling in the infected cell. Neisseria gonorrhoeae activates the extracellular signal-regulated kinase (ERK) signal pathway in epithelial cells through type IV pili. Howie et al. (p. 2715-2721) reveal the pathway of ERK-induced cytoprotection. Activated ERK selectively downregulates two proapoptotic BH3-only proteins, Bad and Bim, through phosphorylation and/or proteasomal degradation. Downregulating either Bad or Bim alone is sufficient to protect the cell from artificially induced apoptosis. The authors discuss the advantage of this cytoprotective mechanism to the pathogen.

"Hypoxia Hypothesis" in Tuberculosis: No Longer Just for Heretics

Based on visual examination of tuberculosis lesions in human patients, pathologists have long pronounced tuberculous granulomas to be hypoxic. The study by Via et al. (p. 2333-2340) reports the first direct evidence that hypoxia is an important characteristic of specific types of tuberculous lesions. In three different species (Guinea pigs, rabbits, and nonhuman primates), caseous necrotic lesions were shown to be hypoxic by using an oncology probe for hypoxia. In rabbits, the bacteria in such lesions were highly sensitive to the anaerobe-specific drug metronidazole, and by insertion of an oxygen-sensitive electrode into lesions in live animals, the degree of hypoxia was quantified. These data support the idea that drugs that can act in anaerobic environments may be necessary for optimal treatment of tuberculosis.

Pneumococcal Protein PcpA Appears To Elicit Immunity against Invasive Disease but Not against Colonization

Immunization of humans with the 7-valent polysaccharide conjugate vaccine (7-VPCV) reduced pneumococcal colonization with the respective capsular types and increased staphylococcal colonization. The effects of 7-VPCV on colonization also selected for non-7-VPCV capsular types, which are rapidly filling the niche left by the vaccine types. Because of differences in local manganese levels, PcpA should be expressed during pneumonia and sepsis but not by pneumococci on the mucosal surface. Glover et. al. (p. 2767-2776) show that immunization with PcpA protected mice against pneumonia and sepsis but not against colonization. Such a human vaccine should not affect staphylococcal colonization or select for pneumococci that escape the vaccine.

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content