Activation of Innate Immunity by Bacterial Ligands of Toll-Like Receptors

Abstract

Tγδ 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 Tγδ 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 Tγδ 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.

Oral microbiota in the oral-genitourinary axis: identifying periodontitis as a potential risk of genitourinary cancers

“…Inflammation has long been associated with cancer pathogenesis. Inflammation is stimulated by innate-immune receptors such as the Toll-like receptors (TLRs) [ 104 ]. The activation of inflammatory signals creates a tumor environment that promotes cancer formation and growth [ 105 ].…”

TLR2/NFκB signalling regulates endogenous IL-6 release from marrow-derived mesenchymal stromal cells to suppress the apoptosis of PC12 cells injured by oxygen and glucose deprivation

“…These results demonstrated that TLR2 expression in MSCs directly affected the expression levels of NFκB and IL-6. NFκB is an important factor in the TLR2 signalling pathway, and exerts a key role in the induction of trans-shipment in the innate immune system (26)(27)(28). The NFκB inhibitor, PDTC, was also used in the present study to treat MSCs.…”

Cell-bound exopolysaccharides of Lactobacillus brevis KB290 enhance cytotoxic activity of mouse splenocytes

“…Akhmatova et al . () showed that bacterial and viral ligands activate the innate immune system of mice. Other studies also showed that heat‐killed probiotic bacteria protected against influenza virus infection by modulating immune functions.…”

“…Some probiotics enhance cell-mediated cytotoxic activity against tumour cells and virus-infected cells; thus, they might help protect hosts from tumour development (Takeda and Okumura 2007) and infectious diseases (Namba et al 2010). Akhmatova et al (2014) showed that bacterial and viral ligands activate the innate immune system of mice. Other studies also showed that heat-killed probiotic bacteria protected against influenza virus infection by modulating immune functions.…”