Figure 5: Hypothesized working model for tonsil hyperplasia.

OSAS is characterized by an irreversible tonsil hyperplasia. Here we hypothesise on one of the mechanisms causing such pathology. GAS-induced tight junction loosening and epithelial damage allow bacteria and/or bacterial virulence factors penetrating the tonsil tissue. GAS colonising tonsillar tissue of OSAS patients produces SLO protein, which interacting with TLR4, induces the production of CysLTs by TMCs. SLO, binding to TLR4, activates the TRIF- and the MyD88-dependent signaling pathway, which respectively to a major (tick arrow) and minor extent (thin arrow) induce p38MAPK activation, resulting in the phosphorylation of cPLA₂, which in turn activates the cascade leading to cysteinyl leukotriene production. This production can be further enhanced by the up-take of CysLTs by its specific receptor 1 expressed by the TMCs involved. The CysLTs produced induce in turn, again via LT1-R expressed by T and B cells, proliferation of tonsillar helper T cells and plasma B cells, leading to the hyperplasia of the tonsils. The mechanism of cell proliferation could be triggered by the direct interaction of CysLTs with receptor 1 both in T and in B cells (green arrows), or by interaction of CysLTs with receptor 1 in T cells, which, when proliferating, could produce cytokines causing plasma B cell proliferation (blue arrows), which would be responsible for the hyperplasia of the germinal centers described in OSAS-GAS cases.