Porin of Shigella dysenteriae directly promotes toll-like receptor 2-mediated CD4+ T cell survival and effector function.
Porin of Shigella dysenteriae type 1 up-regulated Toll-like receptor (TLR)2 on CD3-stimulated CD4(+) T cells but could not induce the expression of other TLRs. TLR2 in association with myeloid differentiating factor 88 (MyD88) triggered the downstream signal transduction pathway leading to activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB), and degradation of IkappaB, the NF-kappaB inhibitor. TLR2 co-stimulation by porin resulted in T cell expansion by inducing both proliferation and survival of the CD4(+) T cells. Extracellular signal-regulated kinase (ERK)1/2 activation inhibitor U0126 and NF-kappaB translocation inhibitor SN-50 significantly inhibited proliferation of T cells, highlighting a direct role of ERK and NF-kappaB in the process. However, cell survival involving Bcl-X(L) induction was found to be regulated essentially by ERK with no significant role of NF-kappaB. Porin-induced proliferation was supported by induction of IL-2 and CD25 that are known to play a pivotal role in T cell expansion. Apart from inducing T cell proliferation, porin triggered effector functions of the cells, evident from TLR2- and MyD88-dependent release of type 1 cytokines tumor necrosis factor (TNF) and interferon (IFN)-gamma along with the induction of type 1 chemokines macrophage-inflammatory protein (MIP)-1alpha and MIP-1beta and their receptor CCR5. The proliferation, survival and effector function of CD4(+) T cells through TLR2 co-stimulation show the capability of porin to directly turn adaptive immunity into action.
Biswas
Amlan
A
Division of Immunology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road, Scheme-XM, Kolkata-700 010, West Bengal, India.
Banerjee
Pallavi
P
Biswas
Tapas
T
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D020868:Gene Silencing; D007093:Imidazoles / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D018272:Porins / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000819:agonists / Q000276:immunology / Q000378:metabolism; D012762:Shigella dysenteriae / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000235:genetics / Q000276:immunology*
D002070:Butadienes; D016207:Cytokines; D004791:Enzyme Inhibitors; C508018:Il2ra protein, mouse; D007093:Imidazoles; D053645:Interleukin-2 Receptor alpha Subunit; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D009570:Nitriles; D010455:Peptides; D018272:Porins; D011725:Pyridines; D034741:RNA, Small Interfering; D019707:Receptors, Chemokine; C118258:SN50 peptide; D051195:Toll-Like Receptor 2; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580