Publication Date:
2013-10-08
Description:
Background: Fungi are the second most abundant type of human pathogens. Invasive fungal pathogens are leadingcauses of life-threatening infections in clinical settings. Toxicity to the host and drug-resistance aretwo major deleterious issues associated with existing antifungal agents. Increasing a host's toleranceand/or immunity to fungal pathogens has potential to alleviate these problems. A host's tolerance maybe improved by modulating the immune system such that it responds more rapidly and robustly in allfacets, ranging from the recognition of pathogens to their clearance from the host. An understandingof biological processes and genes that are perturbed during attempted fungal exposure, colonization,and/or invasion will help guide the identification of endogenous immunomodulators and/or smallmolecules that activate host-immune responses such as specialized adjuvants. Results: In this study, we present computational techniques and approaches using publicly availabletranscriptional data sets, to predict immunomodulators that may act against multiple fungalpathogens. Our study analyzed data sets derived from host cells exposed to five fungal pathogens,namely, Alternaria alternata, Aspergillus fumigatus, Candida albicans, Pneumocystis jirovecii, andStachybotrys chartarum. We observed statistically significant associations between host responsesto A. fumigatus and C. albicans. Our analysis identified biological processes that were consistentlyperturbed by these two pathogens. These processes contained both immune response-inducing genessuch as MALT1, SERPINE1, ICAM1, and IL8, and immune response-repressing genes such asDUSP8, DUSP6, and SPRED2. We hypothesize that these genes belong to a pool of commonimmunomodulators that can potentially be activated or suppressed (agonized or antagonized) in orderto render the host more tolerant to infections caused by A. fumigatus and C. albicans. Conclusions: Conclusions: Our computational approaches and methodologies described here can now be applied to newlygenerated or expanded data sets for further elucidation of additional drug targets. Moreover,identified immunomodulators may be used to generate experimentally testable hypotheses thatcould help in the discovery of broad-spectrum immunotherapeutic interventions. All of ourresults are available at the following supplementary website: http://bioinformatics.cs.vt.edu/~murali/supplements/2013-kidane-bmc.KeywordsHost-oriented therapy, Broad-spectrum target, Immunomodulation,
Electronic ISSN:
1471-2180
Topics:
Biology
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