Relationship between mucosal Th17 and Treg in Nasopharynx-Associated Lymphoid Tissue and Their Association with Pneumococcal Carriage in Children and Adults

Streptococcus pneumoniae is a leading cause of respiratory tract infection in humans. It colonizes human nasopharyngeal mucosa, and pneumococcal carriage is common in young children that may account for the high incidence of pneumococcal disease in this age group. Pneumococcal carriage rate in humans decreases with age. However, the immunological factors that mediate the clearance or persistence of carriage in human nasopharynx remain unclear.  Recent studies in mice suggest Th17 is important in host clearance of S. pneumoniae. We have studied the relationship between frequencies of mucosal Th17 and T regulatory cells (Foxp3+ Treg) in human nasopharynx-associated lymphoid tissue (NALT) and age and their association with pneumococcal carriage in children and adults.  The frequencies of Th17 and Treg in adenotonsillar tissue were significantly higher than in peripheral blood (p<0.01) in both children and adults. There was an inverse correlation between frequencies of Th17 and Treg in adenotonsillar tissue (r=-0.52, p<0.01). Tonsillar Th17 frequency was shown to increase with patient’s age (r=0.62, p<0.01), whereas the Treg frequency inversely correlated with age (r=-0.45, p<0.01). Furthermore, there was a positive correlation between the ratio of Th17/Treg in NALT and age of patients. Also, the Th17/Treg ratio was significantly higher in pneumococcal carriage negative than positive children (p<0.05). Our findings suggest that the balance/ratio of mucosal Th17 and Treg in nasopharynx is a critical determinant of pneumococcal clearance/carriage, and support efforts to promote mucosal Th17 in vaccination strategy against pneumococcal infection in humans.