Haemophilus influenzae resides in tonsils and uses immunoglobulin D binding as an evasion strategy.

Haemophilus influenzae (Hi) causes respiratory tract infections and is also considered to be a commensal, particularly in preschool children. Tonsils from patients (n = 617) undergoing tonsillectomy due to chronic infection or hypertrophy were examined. We found that 51% of tonsils were positive for Hi, and in 95% of cases analyzed in detail (n = 39) Hi resided intracellularly in the core tonsillar tissue. Patients harbored several intracellular unique strains and the majority were nontypeable Hi (NTHi). Interestingly, the isolated NTHi bound soluble immunoglobulin (Ig) D at the constant heavy chain domain 1 as revealed by recombinant IgD/IgG chimeras. NTHi also interacted with B lymphocytes via the IgD B-cell receptor, resulting in internalization of bacteria, T-cell-independent activation via Toll-like receptor 9, and differentiation into non-NTHi-specific IgM-producing cells. Taken together, IgD-binding NTHi leads to an unspecific immune response and may support the bacteria to circumvent the host defense.