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Immune cells express multiple Toll-like receptors (TLRs) that are concomitantly activated by a variety of pathogen products. Although there is presumably a need to coordinate the expression and function of TLRs in individual cells, little is known about the mechanisms governing this process. We show that a protein associated with TLR4 (PRAT4A) is required for multiple TLR responses. PRAT4A resides in the endoplasmic reticulum, and PRAT4A knockdown inhibited trafficking of TLR1 and TLR4 to the cell surface and ligand-induced trafficking of TLR9 to lysosomes. Other cell-surface molecules were expressed normally on immunocytes from PRAT4A-/- mice. There was impaired cytokine production to TLR ligands, except to the TLR3 ligand poly(I:C), and to whole bacteria. Activation of antigen-specific T helper type 1 responses were also defective. Moreover, PRAT4A-/- bone marrow chimeric mice were resistant to lipopolysaccharide-induced sepsis. These results suggest that PRAT4A regulates the subcellular distribution and response of multiple TLRs and is required for both innate and adaptive immune responses.
Pubmed ID: 17998391
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Cell line RAW 264 is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsCell line RAW 264.7 is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus
View all literature mentionsCell line RAW 264 is a Cancer cell line with a species of origin Mus musculus
View all literature mentionsMus musculus with name C57BL/6-PRAT4Atm1Kmiy/KmiyRbrc from IMSR.
View all literature mentionsMus musculus with name C57BL/6-PRAT4Atm1Kmiy/KmiyRbrc from IMSR.
View all literature mentionsMus musculus with name C57BL/6-PRAT4Atm1Kmiy/KmiyRbrc from IMSR.
View all literature mentionsMus musculus with name C57BL/6-PRAT4Atm1Kmiy/KmiyRbrc from IMSR.
View all literature mentionsMus musculus with name C57BL/6-PRAT4Atm1Kmiy/KmiyRbrc from IMSR.
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