GEORGE DEEPE

..Their thought-provoking findings reveal the complexities of vaccine-induced immunity and could be used to improve vaccine efficacy...

..Impaired immunity is not a result of altered cytokine responses or changes in the inflammation and may not be demonstrable in other murine strains...

..The fungi under discussion in this review include Candida spp., Aspergillus spp., Cryptococcus neoformans, Coccidioides spp., Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis and Pneumocystis jirovecii...

..Recent reports indicate that, in humans, treatment with inhibitors of TNF-alpha is associated with disseminated histoplasmosis. Here, I review the mechanisms by which inhibition of TNF-alpha may exacerbate infection with H. capsulatum...

..More importantly, the studies summarized herein demonstrate that understanding the host response to a protein or mutant fungus is critical to creating a vaccine that may be useful for the immunocompromised patient...

..T cells from infected, TNF-alpha-neutralized mice failed to protect T cell-deficient mice. The absence of TNF-alpha induces a defect in T cell-mediated protection...

..Conversely, interferon- gamma levels were decreased. Thus, IL-1 contributes to host resistance to infection with H. capsulatum...

..Antagonism of endogenous cytokine is associated with an enhanced susceptibility to histoplasmosis in both mice and humans. The mechanisms by which TNF-alpha modulates the protective immune response will be discussed...

..Thus, neutralization of TNF-alpha is associated with the induction of a population of regulatory T cells that alter protective immunity in an Ag-specific manner to Histoplasma capsulatum...

..This knowledge can be used to improve treatment as well as diagnosis. Hence, this review summarizes some of the most recent findings regarding host-fungus interaction...

..These results reveal the complex nature of intracellular residence of this fungus. Moreover, the findings demonstrate that there is a skewing in the subpopulations of cells that are infected, especially DC...

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..Memory cell generation was transiently increased in IL-10(-/-) mice, but the protective function conferred by cells from these mice following immunization is strikingly more vigorous than that of wild-type...

..These findings reveal a new mechanism whereby GM-CSF contributes to host protection and demonstrate differences in control of primary and secondary histoplasmosis...

..These results delineate the complexity of the regulatory elements necessary for vaccination against this fungus...

..Elimination of V beta 10(+) and V beta 14(+) cells from naive mice did not alter the course of infection over a period of 21 days. Thus, overexpression of V beta families does not necessarily signify a key role in host defense...

..Thus, a single Vbeta family was essential for vaccine-induced immunity. Moreover, the mechanism by which Vbeta6+ contributed to protective immunity differed between unfractionated splenocytes and T cell clones...

..Thus, F3-mediated protection is confined to a defined Vbeta population, but exacerbation of disease is mediated by multiple Vbeta families...

..Generation of functional IL-17(+) cells is dependent on IL-6 and IL-10. Our findings also establish the existence a regulatory IL-17/IL-23 axis in histoplasmosis...

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..These results suggest that this cytokine may be useful as an adjunctive treatment for histoplasmosis...

..The significance of cytokines and other endogenous soluble mediators to the protective immune response have been analyzed. Moreover, work concerning the relative importance of T cell subsets to protective immunity has been initiated...

..The data reveal the complex control by the host to prevent reactivation of this fungus...

..Thus, apoptosis is a critical element of protective immunity to H. capsulatum. Production of IL-4 and IL-10 is markedly elevated when apoptosis is inhibited, and the release of these cytokines exacerbates the severity of infection...

..These results indicate that the cytokine milieu influences the shape of the T-cell receptor repertoire and support the importance of gamma interferon and interleukin-10 in the efficacy of heat shock protein 60...

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..Furthermore, CD4(+) T cells had a deleterious impact on immunity in infected CCR2(-/-) mice...

..These data indicate that a distinct subset of Vbeta8.1/8.2(+) T cells is crucial for the generation of a protective response to rHsp60...

..Furthermore, increased phagocyte-derived IL-4 in CCR2(-/-) mice is associated with the presence of alternatively activated phagocytic cells...

..Thus, both in vitro and in vivo data demonstrate that IFN-gamma is essential for up-regulation, but not constitutive expression, of immunoproteasome subunits in mice...

..Thus, CCR5 dictates pathogen persistence by tightly regulating the balance between Treg and Th17 cells in H. capsulatum infection...

..capsulatum by delaying clearance of the organism but does not prevent the generation of a Th1 response that ultimately controls infection...

..We conclude that PA28gamma(-/-) mice, like PA28alpha(-/-)/beta(-/-) mice, are deficient in the processing of only specific Ags...

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..The lethality was dependent on the kinase activity of hygromycin phosphotransferase. These results should raise awareness of the potential detrimental effects of the hph gene...

..Treatment of cells with GM-CSF altered the host Zn(2+) binding species profile. These results establish that Zn(2+) deprivation may be a host defense mechanism utilized by macrophages...

..Thus, a homologue of Sec31 is a trigger of the expansion of the V beta 4+ T cell population and is important to the generation of protective immunity...

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..Th1 responses are central to limiting infection with many fungi; thus, a great deal of attention has been focused recently on the antigen(s) that trigger such a response...

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..3 and 92.5%, respectively) for HSP60 suggested that the recombinant protein can be used singly or in association with other recombinant antigens to detect antibody responses in P. brasiliensis-infected patients...

..CD4(+) cells were necessary for the efficacy of the vaccination in both the afferent and efferent phases. Thus, we have demonstrated that this immunodominant antigen is a candidate for the development of a vaccine against this fungus...

..The recombinant 45-kDa protein was shown to be catalytically active; FMD activity was detected in P. brasiliensis yeast and mycelium...

..Thus, the outgrowth of protective T-cell clones against immunodominant antigens of B. dermatitidis is biased by a combination of the TCR repertoire and Th1 cytokine production...

..This rapid, sensitive, and specific assay provides a way to identify typical and atypical isolates of H. capsulatum var. capsulatum...

..A recombinant protein was generated in Escherichia coli. Our data suggest that PbYmnt encodes one member of a glycosyltransferase family of proteins and that our strategy was useful in the isolation of differentially expressed genes...

..The data presented in this supplement highlight the need for further research into these key areas, and illustrate our current understanding of the mode of action of TNF blockers as only the tip of the iceberg...

..rhsp 60 serves as a paradigm, and the data emerging from this proposal may be broadly applicable to other antigens against intracellular pathogens. ..

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..Our work will demonstrate how important it is for lymphocytes and macrophages to die in order that the host can survive. ..

..Our work will demonstrate how important it is for lymphocytes and macrophages to die in order that the host can survive. ..

..Our work will demonstrate how important it is for appropriate signaling through a surface receptor for a particular chemokine in order that the host can survive. ..

..Thus, it may be possible to correlate the functional activity of T cells with their expression of specific T cell receptor family. Furthermore, HIS-62 and HIS-80 may serve as a paradigm for the interaction of Hc antigens with T cells...

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..Our work will demonstrate how important it is for lymphocytes and macrophages to die in order that the host can survive. ..