Porin of Shigella dysenteriae enhances mRNA levels for Toll-like receptor 2 and MyD88, up-regulates CD80 of murine macrophage, and induces the release of interleukin-12.
Sera of patients convalescing from shigellosis reacted strongly and specifically with the 38,000 Da monomer of porin of Shigella dysenteriae type 1. Since human, the only natural host of S. dysenteriae type 1, recognized the protein through humoral immune response, it is of great significance to study the surface-exposed outer membrane antigen as an adjuvant. Porin treatment of CD11b+ peritoneal cavity (PerC) MPhi of BALB/c mouse was found to up-regulate CD80 on cell surface and had no effect on CD86 expression. The surface expression of CD80 got increased by 1.6-fold in the presence of gamma interferon (IFN-gamma) supporting selective regulation of the B7-1 (CD80) member of the B7 family. MPhi released 7.25 pg of interleukin-12 (IL-12) in the presence of porin. The protein in combination with IFN-gamma augmented profoundly the release of IL-12 by 2.6-fold. Porin-mediated induction of IL-12 release would therefore influence Th1-type response, known to be preferentially triggered due to up-regulation of CD80 expression. Treatment of PerC MPhi by the protein showed an increase of mRNA for both Toll-like receptor (TLR)2 and myeloid differentiation factor 88 (MyD88) by 2- and 2.3-fold respectively, emphasizing that TLR2 is essential for recognition of S. dysenteriae type 1 porin. Understanding the mechanism of adjuvanticity of porin of S. dysenteriae type 1 is a necessary step towards the development of a better adjuvant against shigellosis.
Ray
Avijit
A
National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road, Scheme XM, Kolkata-700 010, West Bengal, India.
Chatterjee
Nabendu S
NS
Bhattacharya
Sujit K
SK
Biswas
Tapas
T
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D015153:Blotting, Western; D004405:Dysentery, Bacillary / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D017737:Macrophages, Peritoneal; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D053594:Myeloid Differentiation Factor 88; D018272:Porins / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012762:Shigella dysenteriae / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D015854:Up-Regulation
D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D018272:Porins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D018664:Interleukin-12