Is the oral microbiome a source to enhance mucosal immunity against infectious diseases?

Abstract

Mucosal tissues act as a barrier throughout the oral, nasopharyngeal, lung, and intestinal systems, offering first-line protection against potential pathogens. Conventionally, vaccines are applied parenterally to induce serotype-dependent humoral response but fail to drive adequate mucosal immune protection for viral infections such as influenza, HIV, and coronaviruses. Oral mucosa, however, provides a vast immune repertoire against specific microbial pathogens and yet is shaped by an ever-present microbiome community that has co-evolved with the host over thousands of years. Adjuvants targeting mucosal T-cells abundant in oral tissues can promote soluble-IgA (sIgA)-specific protection to confer increased vaccine efficacy. Th17 cells, for example, are at the center of cell-mediated immunity and evidence demonstrates that protection against heterologous pathogen serotypes is achieved with components from the oral microbiome. At the point of entry where pathogens are first encountered, typically the oral or nasal cavity, the mucosal surfaces are layered with bacterial cohabitants that continually shape the host immune profile. Constituents of the oral microbiome including their lipids, outer membrane vesicles, and specific proteins, have been found to modulate the Th17 response in the oral mucosa, playing important roles in vaccine and adjuvant designs. Currently, there are no approved adjuvants for the induction of Th17 protection, and it is critical that this research is included in the preparedness for the current and future pandemics. Here, we discuss the potential of oral commensals, and molecules derived thereof, to induce Th17 activity and provide safer and more predictable options in adjuvant engineering to prevent emerging infectious diseases.

Fig. 1. Mechanisms of traditional vaccine versus mucosal induction of cell and serum mediated protection.

A Current adjuvanted vaccines are administered subcutaneously and induce primarily a Th2 mediated cellular and pronounced IgG antibody response. B Experimental adjuvants seeking Th17 protection elicit primarily Th1(1) sometimes accompanied by Th17 (2) cell mediated in addition to the IgG response when applied subcutaneously (3). When combined with a mucosal booster, these experimental adjuvants can offer a robust high affinity IgA response that confers additional mucosal protection (1,2). C Experimental adjuvants specific for Th17 can also elicit robust serum IgG when administered via mucosal tissue (4) along with robust Th17 and mucosal IgA with utilization of pIgR (3). Sources^–.

Fig. 2. Direct and Indirect antigens derived from P. gingivalis in induction of T-cell functions.

In the left panel mFA is shown to induce a Th2 response whereas FimA elicits Th1 activity, it is not known if these effects are direct or indirect but FimA can signal through TLR2 to upregulate NO and CD11b/CD18 integrin expression. FimA also acts as a ligand to the CD11b/CD18 integrin. In the right panel, the products that purify out from the LPS-extraction method are shown; antagonist and agonist LPS (pink and purple) and the lipoprotein from gene product PG1828 (orange). Together, this ‘LPS’ can elicit CD4 T-cell, and Th17 expansion as well as IL-17 from γδTc subsets. Although the signaling pathways for T-cell induction are not yet identified, LPS typically signals through TLR4 but can also be presented (lipid A) by DCs via CD1b or CD1c.