Commensals, Pathogens, and Immunity from the perspective of oropharyngeal mucosae

L SARMIENTO VARON; J PUYSSEGUR; R PASTOR; P FERNANDEZ; CM BARBERIS; ME ARABOLASA; B PAOLI; EI ARANA

Varadero

Congreso; 13th Latin American and Caribbean Congress of Immunology ALACI.; 2022

Human paired palatine tonsils are lymphoid epithelial tissues of the oral mucosa around the oropharynx. We have used them as a model to explore the oropharyngeal mucosal immune system as well as to study basic aspects of B cell biology. While tonsillar hyperplasia is the most frequent cause of tonsillectomy in children younger than 10, abscesses and acute infections are responsible for most tonsillectomies in pre-teen and teenagers. Age-related functional changes were explored in our cohort of patients by scoring the percentage of germinal center B cells (BGC) within isolated tonsillar mononuclear cells, as a read out of the effector immunological activity of these organs. We found that the proportion of BGC steadily declined with increasing age. Moreover, we showed that the impairment of GC reaction with ageing, correlated with an increment in the proportion of regulatory B cells. On the other hand, by restraining samples to those of children before puberty operated due to hypertrophied tonsils, we uncovered the role of resident pro-inflammatory B and T cells in sustaining tonsillar hypertrophy and hyperplasia, by producing considerable amounts of TNFwhen challenged. We also showed a relevant proportion of tonsillar Th17 co-expressing TNFas it has been previously reported for other sites of inflammation. Finally, by combining bacterial culture from the tonsillar core of the latter patient´s cohort and subsequent identification of the respective isolates, we determined the most prevalent species. Although the isolated species are considered normal oropharyngeal commensals in children, we confirmed their capacity to breach the epithelial barrier by FISH in tissue biopsies. Therefore, the progression on the cause of tonsillar disease with age might illustrate the adaptation of this mucosal tissue to constant inflammation due to undetected persistent infection. These results underscore the importance of the interplay between the host immune system and the commensal microorganisms able to switch from asymptomatic colonization to invasive disease.