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Oral Mucositis: An Update on Innate Immunity and New Interventional Targets.

ABSTRACT: Oral mucositis (OM), a common debilitating toxicity associated with chemo- and radiation therapies, is a significant unmet clinical need for head and neck cancer patients. The biological complexities of chemoradiotherapy-induced OM involve interactions among disrupted tissue structures, inflammatory infiltrations, and oral microbiome, whereby several master inflammatory pathways constitute the complicated regulatory networks. Oral mucosal damages triggered by chemoradiotherapy-induced cell apoptosis were further exacerbated by the amplified inflammatory cascades dominantly governed by the innate immune responses. The coexistence of microbiome and innate immune components in oral mucosal barriers indicates that a signaling hub coordinates the interaction between environmental cues and host cells during tissue and immune homeostasis. Dysbiotic shifts in oral microbiota caused by cytotoxic cancer therapies may also contribute to the progression and severity of chemoradiotherapy-induced OM. In this review, we have updated the mechanisms involving innate immunity-governed inflammatory cascades in the pathobiology of chemoradiotherapy-induced OM and the development of new interventional targets for the management of this severe morbidity in head and neck cancer patients.

SUBMITTER: Chen C

PROVIDER: S-EPMC7443999 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: Pruritic scabies lesions caused by Sarcoptes scabiei burrowing in the stratum corneum of human skin facilitate opportunistic bacterial infections. Emerging resistance to current therapeutics emphasizes the need to identify novel targets for protective intervention. We have characterized several protein families located in the mite gut as crucial factors for host-parasite interactions. Among these multiple proteins inhibit human complement, presumably to avoid complement-mediated damage of gut epithelial cells. Peritrophins are major components of the peritrophic matrix often found in the gut of arthropods. We hypothesized that a peritrophin, if abundant in the scabies mite gut, could be an activator of complement. METHODOLOGY/PRINCIPAL FINDINGS: A novel full length scabies mite peritrophin (SsPTP1) was identified in a cDNA library from scabies mites. The amino acid sequence revealed four putative chitin binding domains (CBD). Recombinant expression of one CBD of the highly repetitive SsPTP1 sequence as TSP-hexaHis-fusion protein resulted in soluble protein, which demonstrated chitin binding activity in affinity chromatography assays. Antibodies against a recombinant SsPTP1 fragment were used to immunohistochemically localize native SsPTP1 in the mite gut and in fecal pellets within the upper epidermis, co-localizing with serum components such as host IgG and complement. Enzymatic deglycosylation confirmed strong N- and O-glycosylation of the native peritrophin. Serum incubation followed by immunoblotting with a monoclonal antibody against mannan binding lectin (MBL), the recognition molecule of the lectin pathway of human complement activation, indicated that MBL may specifically bind to glycosylated SsPTP1. CONCLUSIONS/SIGNIFICANCE: This study adds a new aspect to the accumulating evidence that complement plays a major role in scabies mite biology. It identifies a novel peritrophin localized in the mite gut as a potential target of the lectin pathway of the complement cascade. These initial findings indicate a novel role of scabies mite peritrophins in triggering a host innate immune response within the mite gut.

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Oral Mucositis: An Update on Innate Immunity and New Interventional Targets.

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