Infection and Immunity, May 2009, p. 1721-1722, Vol. 77, No. 5
0019-9567/09/$08.00+0 doi:10.1128/IAI.00307-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
| SPOTLIGHT |
Articles of Significant Interest Selected from This Issue by the Editors
Anthrax Edema Toxin Promotes Dendritic Cell Maturation and MigrationBacillus anthracis produces and secretes two toxins that contribute to virulence by impairing host immune responses. One of these toxins, edema toxin (ET), impairs host defenses by raising cellular cyclic AMP levels. Maldonado-Arocho and Bradley (p. 2036-2042) demonstrate that ET promotes maturation of dendritic cells (DCs) and enhances their ability to migrate towards the lymph node-homing chemokine macrophage inhibitory protein 3β. Interestingly, cotreatment with the second toxin, lethal toxin, alters ET-induced maturation of DCs but does not inhibit ET-induced migration. This work reveals a mechanism by which ET impairs normal innate immune function and may explain the reported adjuvant effect of ET.
sit Genes Enhance Intracellular Replication and Virulence of Shigella flexneri
The sitABCD genes encode a ferrous iron and manganese transporter that is common among Shigella spp. and Escherichia coli strains that have an intracellular lifestyle. Fisher et al. (p. 1992-1999) show that the sit operon is located on an unstable pathogenicity island in S. flexneri. Comparing a sit mutant with the wild type, they show that Sit provides a competitive advantage to S. flexneri growing within epithelial cells. Further, a sit mutant is attenuated in the mouse lung model but induces a protective immune response.
Selective Advantage for Staphylococcus aureus To Produce Superantigens
Superantigens (SAg) are a family of proteins that corrupt the immune response by triggering aberrant T-cell activation via binding to the variable Vβ region of the T-cell receptor outside the conventional peptide-binding site. Thomas et al. (p. 2043-2050) have determined the Vβ specificities of all known SAg produced by Staphylococcus aureus. They found that each SAg induced the expansion of distinct Vβ subsets (sometimes with redundancies) and that each human Vβ was stimulated by at least one SAg. These findings reveal a broad adaptation of S. aureus to the human immune system, which may provide a selective advantage for S. aureus colonization and persistence.
Validation of an Animal Model for Studying Rheumatic Heart Disease
Rheumatic heart disease (RHD), resulting from group A streptococcal infection, is a uniquely human condition, and until recently, the development of an animal model of RHD was problematic. Gorton et al. (p. 2177-2183) characterize humoral and cellular responses in the rat autoimmune valvulitis (RAV) model and provide further evidence that this model displays valvular and myocardial pathologies similar to those observed in patients with RHD. Their study confirms the suitability of the RAV model for determining the immunopathogenic mechanisms associated with development of RHD.
The Ehrlichia chaffeensis Tandem Repeat Protein Is Involved in a Complex Network of Host Cell Interactions
Ehrlichia chaffeensis survives in mononuclear phagocytes by exploiting and modulating a variety of cellular processes, but the ehrlichial effector proteins involved are unknown. In this study, Wakeel et al. (p. 1734-1745) have determined that p47, a secreted, differentially expressed, tandem repeat protein, interacts with multiple host targets associated with cell signaling, transcriptional regulation, and vesicle trafficking, demonstrating involvement in a complex network of host interactions. Furthermore, this study provides a new insight into the molecular and functional distinctions of dense-cored ehrlichiae, as well as the molecular characteristics of an effector protein involved in facilitating ehrlichial survival in mononuclear phagocytes.
Variant-Specific Immunity Controls Susceptibility to Malaria in Pregnant Mice
Women are susceptible to pregnancy-associated Plasmodium falciparum malaria (PAM), as the parasites can evade preexisting immunity by expressing distinct, pregnancy-specific variant surface antigens on infected erythrocytes. These antigens appear largely synonymous with a member of the PfEMP1 adhesins encoded by the var gene family. However, Megnekou et al. (p. 1827-1834) show that a similar process appears to govern susceptibility to pregnancy-related P. berghei recrudescence in immune mice, despite the absence of var orthologs from the genome of that parasite. This study underscores the general importance of variant-specific immunity as a determinant of clinical outcome of malaria infection and indicates a relevant and convenient animal model of PAM pathogenesis and immunity.
Langerhans Cell Deficiency Impairs Ixodes scapularis Modulation of Th1 Responses in Mice
Ixodes scapularis ticks transmit several human pathogens, including the Lyme disease spirochete, Borrelia burgdorferi. In mice, tick feeding skews T-helper (Th) cell differentiation towards Th2 cells in secondary lymphoid organs through unknown mechanisms. Using mice selectively deficient in epidermal Langerhans cells, Vesely et al. (p. 1881-1887) demonstrate a requirement for this dendritic cell subset in tick-mediated attenuation of Th1 responses in lymph nodes. This requirement is alleviated when Borrelia burgdorferi is introduced by feeding ticks. These findings provide insight into the cellular mechanisms of tick-mediated Th-cell modulation and show that a tick-transmitted pathogen can override this effect.
Human Immunoglobulin E Responses to Paramyosin Are Associated with Protection from Schistosomiasis
Schistosomiasis currently infects an estimated 200 million individuals in the developing world despite decades of drug control efforts, thus mandating alternative control strategies, such as vaccine development. Jiz et al. (p. 2051-2058) have characterized isotype-specific antibody responses to several vaccine candidates and relate them to resistance to reinfection of a cohort of Schistosoma japonicum-infected individuals in The Philippines. They demonstrate that individuals with immunoglobulin E (IgE) but not IgG4 responses to paramyosin have a 77%-lower incidence of reinfection than individuals with only IgG4 responses. These data suggest that optimal vaccine efficacy for S. japonicum paramyosin requires an IgE-specific response that avoids detrimental IgG4 responses.
Infection and Immunity, May 2009, p. 1721-1722, Vol. 77, No. 5
0019-9567/09/$08.00+0 doi:10.1128/IAI.00307-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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