A filarial nematode secreted product differentially modulates expression and activation of protein kinase C isoforms in B lymphocytes.
Filarial nematodes, parasitic worms that cause elephantiasis, chronic skin lesions, and blindness in the tropics, release a number of molecules, some of which appear to be immunomodulatory/suppressive, into the host environment. Here we demonstrate that ES-62, a phosphorylcholine-containing glycoprotein released by the rodent filarial parasite Acanthocheilonema viteae, interferes with activation of B lymphocytes by differential modulation of protein kinase C isoform expression. Indeed, while ES-62 selectively down-regulates expression of the alpha, beta, iota/lambda, delta, and zeta isoforms of PKC, it up-regulates expression of PKC-gamma and -epsilon in B cells. Inhibitor studies suggest that ES-62 appears to promote down-regulation of PKC isoforms mainly by stimulating proteolytic degradation. ES-62 also disrupts the normal activation and nuclear translocation patterns of the alpha and iota/lambda isoforms of PKC following ligation of the Ag receptor. The effects of ES-62 on certain PKC isoforms were found to be modified by coculture with IL-4. Of particular interest was the observation that IL-4 prevented down-regulation of PKC alpha and iota/lambda, isotypes considered to be active in transducing mitogenic signals. Phosphorylcholine-containing secreted products (phosphorylcholine-ES) are also released by human filarial parasites; hence we discuss how these findings may relate to the nature of the human B cell response during filarial infections.
Deehan
M R
MR
Department of Immunology, University of Strathclyde, Glasgow, UK.
Harnett
M M
MM
Harnett
W
W
D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D001692:Biological Transport / Q000276:immunology; D018929:Cell Culture Techniques; D002467:Cell Nucleus / Q000201:enzymology; D004153:Dipetalonema / Q000276:immunology*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D010450:Endopeptidases; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D005849:Gerbillinae; D015801:Helminth Proteins / Q000276:immunology* / Q000378:metabolism; D006868:Hydrolysis; D015847:Interleukin-4 / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000378:metabolism; D013154:Spleen
D015801:Helminth Proteins; D007527:Isoenzymes; D015847:Interleukin-4; D011493:Protein Kinase C; D010450:Endopeptidases