In:
Infection and Immunity, American Society for Microbiology, Vol. 83, No. 4 ( 2015-04), p. 1431-1442
Abstract:
Tuberculosis is a chronic bacterial disease with a complex pathogenesis. An effective immunity against Mycobacterium tuberculosis requires both the innate and adaptive immune responses, including proper T helper (Th) type 1 cell function. FURIN is a proprotein convertase subtilisin/kexin (PCSK) enzyme, which is highly expressed in Th1 type cells. FURIN expression in T cells is essential for maintaining peripheral immune tolerance, but its role in the innate immunity and infections has remained elusive. Here, we utilized Mycobacterium marinum infection models in zebrafish ( Danio rerio ) to investigate how furin regulates host responses against mycobacteria. In steady-state furinA td204e/+ fish reduced furinA mRNA levels associated with low granulocyte counts and elevated Th cell transcription factor expressions. Silencing furin genes reduced the survival of M. marinum -infected zebrafish embryos. A mycobacterial infection upregulated furinA in adult zebrafish, and infected furinA td204e/+ mutants exhibited a proinflammatory phenotype characterized by elevated tumor necrosis factor a ( tnfa ), lymphotoxin alpha ( lta ) and interleukin 17a/f3 ( il17a/f3 ) expression levels. The enhanced innate immune response in the furinA td204e/+ mutants correlated with a significantly decreased bacterial burden in a chronic M. marinum infection model. Our data show that upregulated furinA expression can serve as a marker for mycobacterial disease, since it inhibits early host responses and consequently promotes bacterial growth in a chronic infection.
Type of Medium:
Online Resource
ISSN:
0019-9567
,
1098-5522
DOI:
10.1128/IAI.03135-14
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2015
detail.hit.zdb_id:
1483247-1
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