<i>Haemophilus influenzae</i> and <i>Streptococcus pyogenes</i> Group A Challenge Induce a Th₁ Type of Cytokine Response in Cells Obtained from Tonsillar Hypertrophy and Recurrent Tonsillitis

Abstract

We have previously shown that tonsil tissue both from children with tonsillar hypertrophy and recurrent tonsillitis is colonized and invaded by Haemophilus influenzae and Streptococcus pyogenes group A. In order to evaluate if these bacteria are involved in the immunopathogenesis of these two conditions, tonsillar cells from both groups were stimulated in vitro with intact, heat-inactivated H. influenzae or S. pyogenes A. The immunoreactivity was evaluated by assessing the induction of cytokine production (IL-1α, IL-1β, TNF-α, IL-6, IL-8, IL-2, IFN-γ, IL-4, TNF-β and IL-10), which was detected at the single-cell level. All cytokines studied except IL-4 were induced in both groups after stimulation with H. influenzae or S. pyogenes A. The dominating cytokines were IL-1β, IFN-γ and TNF-β. No major differences in the cytokine pattern or number of cytokine-producing cells were noticed between the two patient cohorts after H. influenzae stimulation. Activation by S. pyogenes A bacteria gave rise to higher frequencies of IFN-γ- and TNF-β-synthesizing cells in the recurrent tonsillitis group. The incidence of CD4-, CD8-positive T cells and CD40-positive B cells was comparable between the two groups while the MAC-387-positive macrophages were significantly higher in the recurrent tonsillitis groups. In conclusion, a Th₁ type of cytokine response was found in both groups following stimulation with H. influenzae or S. pyogenes A.

The association of sore throat and psoriasis might be explained by histologically distinctive tonsils and increased expression of skin-homing molecules by tonsil T cells

“…A number of studies have shown increased expression of cytokines by T cells from RT compared with HT tonsils, with a predominance of Th1 over Th2 cytokines [43][44][45]. When cells from HT and RT tonsils were stimulated with intact, heat-inactivated Haemophilus influenzae and Group A Streptococcus, H. influenza induced IL-1α, IL-1β, tumour necrosis factor (TNF)-α, IL-6, IL-8, IL-2, interferon (IFN)-γ, TNF-β and IL-10 production in both tonsil groups, but Group A Streptococcus induced significantly higher frequencies of IFN-γ-positive cells in the RT group [46]. Similar findings emerged when T cells from HT and RT tonsils were stimulated with isolated streptococcal M-protein, with S. pyogenes-positive RT tonsil T cells secreting more IFN-γ [45].…”

Production of cytokines by mononuclear cells of hypertrophic adenoids in children with otitis media with effusion

“…Different cytokines play key roles in innate immunity to different classes of microbes. Agren et al reported that H. influenzae induced Th1 cytokines in human tonsillar lymphocytes [15]. Harimaya et al demonstrated that Alloiococcus otitidis induced the activation of lymphocytes and the release of Th1 promoting cytokines (IL-12 and IFN-g) during the early phase of the immune response [16].…”

Adaptive Immunity against Streptococcus pyogenes in Adults Involves Increased IFN-γ and IgG3 Responses Compared with Children

“…A previous study indicated the presence of anti-GAS Th1 T cells, but, as whole bacteria were used in their stimulation assays, it cannot be excluded that the observed responses in part derived from innate cells (32). Regarding responses against single proteins, CD4 T cells (directed against GAS M protein) are found in tonsils of patients with recurrent tonsillitis and tonsillar hypertrophy, and these CD4 T cells proliferate and produce cytokines (IFN-g, IL-2, IL-4, IL-5, and IL-6) (33).…”