Stefan H E Kaufmann

..Despite many discordant discussions in the initial phase after these discoveries, innate and adaptive responses are now known to be complementary partners in producing robust immunity...

..Our data demonstrate that protective immune responses can be generated independently of SLO during MTB infection and implicate local pulmonary T-cell priming as a mechanism contributing to host defense...

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..1 surface expression. Thus, we present first evidence that NK1.1 surface expression on liver iNKT cells is reversible during L. monocytogenes infection, and that different mechanisms underlie stimulation by TCR and IL-12...

..However, during TB, MTB promotes NLRP3- and caspase-1-independent IL-1? release in myeloid cells recruited to lung parenchyma and thus overcomes NLRP3 deficiency in vivo in experimental models...

..Our data provide evidence that deregulated innate responses trigger excessive lung inflammation and demonstrate a pivotal role of CARD9 signaling in autonomous innate host defense against tuberculosis...

..Our data provide new insights into the functional competence of NKT cells which will facilitate a better understanding of their versatile role during immune responses...

..We identified several markers unique for different stages of disease progression and not previously associated with virulence-specific host responses in tuberculosis...

..Thus, a combination of host susceptibility and M. tuberculosis virulence determines the role of iNOS in the protection and control of inflammation...

..These data suggest that serine protease activity acts as a protective mechanism within hypoxic regions of lung granulomas and present a potential new strategy for the treatment of tuberculosis...

..enterica Typhimurium and L. monocytogenes...

..Our results demonstrate that in the ST infection model, MyD88 as well as TLR2 and TLR4 were largely dispensable for the induction of protective acquired immunity...

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..Thus, by altering effector T-cell populations differentially, ICOS signaling modulates TB control in the late stage of infection...

..Overall, these results indicate that not only primary T cell responses, but also secondary T cell responses, highly depend on the lymphoid environment for effective activation...

..Although further studies on volatiles from detectable growth phases of Mtb are vital for identification of Mtb-specific volatiles detected by rats, our study underline the potential of C. gambianus for TB diagnosis...

..Our data support expression of Mtb latency associated antigens by rBCG to improve protection against Mtb...

..The aim of this study was to explore whether modulation of the proteasomal activity is a suitable therapeutic approach to limit inflammation in colitis...

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..Thus, specific host defence effectors of activated macrophages directly target a specific virulence function of mycobacteria...

..Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future...

..Moreover, we outline our attempts to develop biomarkers, which could help the monitoring of TB clinical trials, provide the basis for new diagnostics, and allow prognosis of outcome of infection and of drug treatment...

..As a corollary, we assume that a set of biomarkers will be required, termed a biosignature...

..The identified proteins were characterized with regard to biological functions and physicochemical properties providing further evidence for the high efficiency of the prefractionation method described herein...

..Therefore, we also provide approved protocols for selective and efficient extraction of cytosolic, secreted, and hydrophobic plasma membrane proteins of mycobacteria, as well as for isolation of mycobacteria from infected macrophages...

..This can be achieved by using an inducible reporter, choosing the appropriate promoter, and reconstituting mice lacking cells of interest by injecting gene-modified Pax5 deficient pro-B cells...

..T-cell responses against dormancy-, resuscitation-, and reactivation-associated antigens of Mycobacterium tuberculosis are candidate biomarkers of latent infection in humans...

..These results have important implications for the rational design and development of efficacious recombinant subunit vaccines...

..tuberculosis rather than the strength of protection. Our data question the measurement of IFN-gamma secretion by CD4(+) T cells and emphasize the need for new biomarkers for evaluation of tuberculosis vaccine efficacies...

..Such insights should inform us how to design more effective vaccination strategies against intracellular pathogens...

..The generated transcriptome data can be exploited for design of new drugs, especially against multidrug-resistant (MDR) strains, development of more efficient vaccines, and identification of biomarkers for better diagnosis...

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..The recombinant ?ureC hly+ BCG (rBCG) is more efficient than parental BCG (pBCG) against pulmonary TB in preclinical studies and has proven safe and immunogenic in phase I clinical trials...

..The live mutants of Mycobacterium tuberculosis show great promise, but face a myriad of regulatory challenges...

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..Therefore, clonal expansion of CD8(+) T(EF) occurs in childhood TB with potential impact on course and severity of disease...

..Finally, we show the inhibition of M. tuberculosis growth by DHBP in a mouse macrophage model...

..tuberculosis and the latter's dissemination to other organs...

..tuberculosis-infected healthy donors, and (3) noninfected healthy donors...

..Our approach demonstrates the feasibility of identifying minute but distinct differences between isogenic strains and illustrates the consequences of single point mutations on the survival stratagem of M. tuberculosis...

..Furthermore, suppression of protection by cotransferred regulatory T cells was neither accompanied by a general increase of IL-10 expression nor by higher numbers of IL-10-producing CD4+ T cells...

..Finally, future studies will show whether in the firmament of immunology stellate cells will represent fixed or falling stars...

..In particular, these include broad-acting vaccines composed of protein antigens shared by all members of a given pathogen group but absent in the human host and vaccines which operate via T-cells...

..The pipeline of new vaccine candidates from preclinical to clinical testing could be accelerated by development of biomarkers that can predict the clinical outcome of tuberculosis...

..HCMV present in antigen-presenting cells thus blunts the immune response by the blockage of CD1 molecules...

..This review focuses on the multiple mechanisms that govern T cell differentiation during infection...

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..The relevance of these proteins as factors enabling intracellular survival of M. tuberculosis is being discussed...

..The method is robust, easy to perform, inexpensive, and results after reuse are of comparable accuracy to new arrays...

..Our combined approach reveals certain signatures of M. tuberculosis residing within macrophage cells, including the induction of genes involved in DNA damage repair, fatty acid degradation, iron metabolism, and cell wall metabolism...

..Our findings emphasize that alternative activation deprives macrophages of control mechanisms that limit mycobacterial growth in vivo, thus supporting intracellular persistence of M. tuberculosis...

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..Such insights could lead to future interventions to address TB as a global health issue...

..We review recent advances in TB research within the context of this ambitious view of TB...

..Although tuberculosis research was instrumental in the birth of immunology, the two disciplines soon separated. The time is ripe for a reunion. Immunology has much to offer for rational intervention measures toward tuberculosis control...

..Granulysin produced by cytolytic T cells directly contributes to immune defense against tuberculosis (TB). We investigated granulysin as a candidate immune marker for childhood and adolescent TB...

..Long-term vaccination strategies need to target these more ambitious goals. Even though vaccine development will have a price, the return of investment will greatly exceed original costs...

..Hence, they are not only the founders of immunology but also were the first to envisage infection biology as the result of an interplay between host and pathogen...

..Up to 1000-fold linear RNA amplification in a single amplification round was obtained. To our knowledge, this study describes the first amplification method for mycobacterial RNA...

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..tuberculosis infection. Taken together, we propose the detour pathway to represent a genuine immunological mechanism mediating crosspriming of CD8 T cells in vivo and protection against tuberculosis...

..Local expression of IFN-gamma in the lung increases markers of allergic airway inflammation, but decreases airway hyperresponsiveness in a murine model of allergic-asthma...

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..1- T-cell subset to antibacterial protection is covered by more profound detrimental effects of the NK1.1+ T-cell subset...

..Our data establish: (a) defective iron metabolism explains the increased susceptibility of beta2m-KO mice over MHC-I-KO mice, and (b) iron overload represents an exacerbating cofactor for tuberculosis...

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..Thus, functional participation of slfn8 in the regulatory networks governing T cell development and growth appears to be cell type specific...

..HNP-1 rescued murine macrophages from B. anthracis-induced cytotoxicity, and in vivo treatment with HNP-1-3 protected mice against the fatal consequences of LeTx...

..Most importantly, DNA vaccination induced protection against an otherwise lethal dose of L. monocytogenes...

..This important new function of cell death in antibacterial immunity requires consideration for rational vaccine design...

..Therefore, marginal zone macrophages and marginal metallophilic macrophages are crucial for trapping of particulate Ag but dispensable for Ag presentation...

..Our data point to a novel role of LFA-1 in control of the proinflammatory/anti-inflammatory cytokine network...

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..Here, we discuss how pathogens compete with the host for iron, and also how the host uses iron to counteract this threat...

..These data provide new insights into pathogenesis of the most common forms of pneumonia, highlighting the value of transcriptional profiling for the elucidation of underlying mechanisms...

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..These findings lead to a revised view of the regional immune response in human tuberculosis. Novel insights into this dynamic cross-talk form the basis of novel intervention strategies...

..Despite great efforts, however, Koch failed to conquer tuberculosis, which still causes enormous health problems worldwide 100 years after his Nobel award...

..We concluded that superior vaccine efficacy of DeltaureC hly+ rBCG as compared with parental BCG is primarily based on improved cross-priming, which causes enhanced T cell-mediated immunity...

..tuberculosis and the infected host, the nature of protective immune responses, adaptation of the bacillus to host-imposed stresses, animal models, and new techniques...

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