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Secretome: clues into pathogen infection and clinical applications.

ABSTRACT: The secretome encompasses the complete set of gene products secreted by a cell. Recent studies on secretome analysis reveal that secretory proteins play an important role in pathogen infection and host-pathogen interactions. Excretory/secretory proteins of pathogens change the host cell environment by suppressing the immune system, to aid the proliferation of infection. Identifying secretory proteins involved in pathogen infection will lead to the discovery of potential drug targets and biomarkers for diagnostic applications.

SUBMITTER: Ranganathan S

PROVIDER: S-EPMC2808748 | biostudies-other | 2009 Nov

REPOSITORIES: biostudies-other

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Secretome: clues into pathogen infection and clinical applications.

Ranganathan Shoba S Garg Gagan G

Genome medicine 20091130 11

The secretome encompasses the complete set of gene products secreted by a cell. Recent studies on secretome analysis reveal that secretory proteins play an important role in pathogen infection and host-pathogen interactions. Excretory/secretory proteins of pathogens change the host cell environment by suppressing the immune system, to aid the proliferation of infection. Identifying secretory proteins involved in pathogen infection will lead to the discovery of potential drug targets and biomarke ...[more]

PMID: 19951402

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Project description:PurposeCoccidioidomycosis (CM) is a systemic fungal disease caused by the dimorphic fungi Coccidioides immitis and Coccidioides posadasii. In its endemic areas of the United States, CM is growing as a public health challenge with a marked increase in incidence in the last 15 years. Although Coccidioides infection is asymptomatic in most cases, symptomatic pulmonary disease occurs in ~40% and disseminated coccidioidomycosis (DCM) occurs in ~1% of previously healthy children and adults. DCM is markedly more common in immunocompromised people, who often experience life-threatening disease despite use of antifungal medications. Although options for antifungal therapy have improved, lifelong therapy is needed for those who develop coccidioidal meningitis. The purpose of this article was to review the state of antifungal therapy and recent studies of host-pathogen interactions in CM in light of advances in immunomodulatory therapy.MethodsThe study included a review of PubMed and abstracts of the Coccidioidomycosis Study Group (years 2000-2019).FindingsCurrent therapy for CM relies upon azole and polyene antifungal agents. Murine models and studies of DCM in patients with monogenic primary immunodeficiency states and acquired immunodeficiency have revealed the importance of both innate and adaptive immune responses in the control of infections with Coccidioides species. In particular, defects in sensing of fungi and induction of cellular immune responses have been frequently reported. More recently, polymorphisms in key signaling pathways and in the generation of Th17 and Th1 immune responses have been linked with DCM.ImplicationsAntifungal therapy is sufficient to control disease in most cases of CM, but treatment failure occurs in cases of severe pulmonary disease and nonmeningeal disseminated disease. Lifelong therapy is recommended for meningitis in view of the very high risk of recurrence. Corticosteroid therapy is advised by some experts for severe pulmonary disease and for some neurologic complications of DCM. DCM is only rarely the result of a severe monogenic immunodeficiency. Case studies suggest that reorienting cellular immune responses or augmenting effector immune responses may help resolve DCM. Systematic investigation of immunotherapy for coccidioidomycosis is advisable and may help to address the recent marked increase in reports of the disease in endemic areas.

Dataset Information

Secretome: clues into pathogen infection and clinical applications.

Publications

Secretome: clues into pathogen infection and clinical applications.

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