The Mycoplasma-derived macrophage-activating 2-kilodalton lipopeptide triggers global immune activation on nasal mucosa-associated lymphoid tissues.
A better knowledge on how immune responses are initiated in mucosal tissues would facilitate the design of new mucosal vaccines, as well as improve our understanding on host defense against infection. We investigated the mechanisms of adjuvanticity of the Mycoplasma-derived macrophage-activating 2-kDa lipopeptide (MALP-2), which binds to the heterodimer formed by the Toll-like receptors 2 and 6 (TLR2 and -6), at the level of the murine nasal mucosa-associated lymphoid tissues (NALT). TLR2 expression analysis demonstrated that several cell types from the nasal cavity were able to overexpress this receptor, either constitutively (such as B cells) or after stimulation (i.e., T cells). MALP-2 stimulated a strong B-cell activation. In addition, the antigen presentation capacity of dendritic cells was improved after in vivo loading with antigen in the presence of MALP-2. We also observed an up-regulated expression of activation markers and adhesion molecules on T cells, suggesting that they have enhanced responsiveness and interaction potential. Quantitative reverse transcription-PCR analysis showed that MALP-2 administration resulted in the stimulation of a proinflammatory cascade. We observed an early up-regulated expression of IP-10, MCP-1, MCP-3, MIP-1alpha, MIP-2, and CCR-2 which was reversed within 36 h. The obtained results demonstrated that MALP-2 creates a reversible local microenvironment which promotes effective priming of T and B cells in the NALT.
Rharbaoui
Faiza
F
Vaccine Research Group, Division of Microbiology, GBF German Research Center for Biotechnology, Mascheroder Weg 1, D-38124 Braunschweig, Germany.
Westendorf
Astrid
A
Link
Claudia
C
Felk
Sandra
S
Buer
Jan
J
Gunzer
Matthias
M
Guzmán
Carlos A
CA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D007108:Immune Tolerance; D055666:Lipopeptides; D008213:Lymphocyte Activation / Q000187:drug effects; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000276:immunology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000502:physiology*; D019707:Receptors, Chemokine / Q000235:genetics; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors
D000276:Adjuvants, Immunologic; D055666:Lipopeptides; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; C495369:Tlr6 protein, mouse; D051195:Toll-Like Receptor 2; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors; C106335:macrophage stimulatory lipopeptide 2