PMID- 24634669 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20140317 LR - 20231104 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 5 DP - 2014 TI - Activation of innate immunity by bacterial ligands of toll-like receptors. PG - 89 LID - 10.3389/fimmu.2014.00089 [doi] LID - 89 AB - Tgammadelta and B1 lymphocytes are essential components of the mucosal immune system, activated directly by different bacterial and viral ligands without additional costimulatory signals and preprocessing of other immune effectors. This ability enables the immune system to provide rapid protection against pathogens and contributes to the decoding mechanism of the sensitizing activity of mucosal antigens. The early interaction of these cells results in the production of antibodies of immunoglobulin M (IgM) and IgA isotypes, but not immunoglobulin E (IgE). We studied the subcutaneous, intranasal, and oral delivery as three major routes of potential entry for antigens of opportunistic microorganisms, using the immunomodulator Immunovac-VP-4, which is able to activate Tgammadelta and B1 lymphocytes. The subcutaneous and intranasal routes produced a significant increase of these cells in lymph nodes associated with the nasal cavity (NALT) and in those associated with bronchial tissue (BALT). The oral route significantly increased levels of these cells in the spleen, in NALT, BALT, and in nodes associated with the gut (GALT). We found that mucosal application of Immunovac-VP-4, which contains antigens of conditionally pathogenic microorganisms, in conjunction with the activation of Tgammadelta and B1, induces adaptive immune mechanisms not only in the lymphoid formations associated with the respiratory system and with GALT, but also in the spleen [increased expression of cluster of differentiation 3 (CD3), CD4, CD8, CD19, and CD25]. This indicates that there is migration of lymphoid cells from the regional lymph nodes and mucosal lymphoid tissues via the lymph and blood to distant organs, resulting in lymphoid development, and both local and systemic immunity. Mucosal application of Immunovac-VP-4 in mice potentiates the cytotoxic activity of NK cells in the NALT, BALT, and GALT. The highest cytotoxicity was observed in cells, derived from lymphoid tissue of the intestine after oral immunization. Although we found that cytokine production was increased by all three immunization routes, it was most intensive after subcutaneous injection. Our findings confirm that there is an intensive exchange of lymphocytes not only between lymphoid formations in the mucous membranes of the respiratory tract and of GALT, but also with the spleen, which means that if effective mucosal vaccines are developed, they can induce both local and systemic immunity. FAU - Akhmatova, Nelli K AU - Akhmatova NK AD - Laboratory of Therapeutic Vaccines, I. I. Metchnikov Research Institute for Vaccines and Serum, Russian Academy of Medical Sciences , Moscow , Russia. FAU - Egorova, Nadezhda B AU - Egorova NB AD - Laboratory of Therapeutic Vaccines, I. I. Metchnikov Research Institute for Vaccines and Serum, Russian Academy of Medical Sciences , Moscow , Russia. FAU - Kurbatova, Ekaterina A AU - Kurbatova EA AD - Laboratory of Therapeutic Vaccines, I. I. Metchnikov Research Institute for Vaccines and Serum, Russian Academy of Medical Sciences , Moscow , Russia. FAU - Akhmatov, Elvin A AU - Akhmatov EA AD - Laboratory of Therapeutic Vaccines, I. I. Metchnikov Research Institute for Vaccines and Serum, Russian Academy of Medical Sciences , Moscow , Russia. LA - eng PT - Journal Article DEP - 20140305 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC3942644 OTO - NOTNLM OT - BALT OT - GALT OT - NALT OT - Toll-like receptors OT - bacterial OT - immunovac-VP-4 OT - poly-component p OT - vaccine EDAT- 2014/03/19 06:00 MHDA- 2014/03/19 06:01 PMCR- 2014/01/01 CRDT- 2014/03/18 06:00 PHST- 2013/10/26 00:00 [received] PHST- 2014/02/19 00:00 [accepted] PHST- 2014/03/18 06:00 [entrez] PHST- 2014/03/19 06:00 [pubmed] PHST- 2014/03/19 06:01 [medline] PHST- 2014/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2014.00089 [doi] PST - epublish SO - Front Immunol. 2014 Mar 5;5:89. doi: 10.3389/fimmu.2014.00089. eCollection 2014.