Th17 responses to pneumococcus in blood and adenoidal cells in children

Abstract

Summary Pneumococcal infections cause a large global health burden, and the search for serotype‐independent vaccines continues. Existing conjugate vaccines reduce nasopharyngeal colonization by target serotypes. Such mucosal effects of novel antigens may similarly be important. CD4+ Th17 cell‐dependent, antibody‐independent reductions in colonization and enhanced clearance have been described in mice. Here we describe the evaluation of T helper type 17 (Th17) cytokine responses to candidate pneumococcal protein vaccine antigens in human cell culture, using adenoidal and peripheral blood mononuclear cells. Optimal detection of interleukin (IL)‐17A was at day 7, and of IL‐22 at day 11, in these primary cell cultures. Removal of CD45RO+ memory T cells abolished these responses. Age‐associated increases in magnitude of responses were evident for IL‐17A, but not IL‐22, in adenoidal cells. There was a strong correlation between individual IL‐17A and IL‐22 responses after pneumococcal antigen stimulation (P < 0·015). Intracellular cytokine staining following phorbol myristate acetate (PMA)/ionomycin stimulation demonstrated that > 30% CD4+ T cells positive for IL‐22 express the innate markers γδT cell receptor and/or CD56, with much lower proportions for IL‐17A+ cells (P < 0·001). Responses to several vaccine candidate antigens were observed but were consistently absent, particularly in blood, to PhtD (P < 0·0001), an antigen recently shown not to impact colonization in a clinical trial of a PhtD‐containing conjugate vaccine in infants. The data presented and approach discussed have the potential to assist in the identification of novel vaccine antigens aimed at reducing pneumococcal carriage and transmission, thus improving the design of empirical clinical trials.

Generation of protective pneumococcal-specific nasal resident memory CD4+ T cells via parenteral immunization

“…25,39 Using either live exposure to pneumococcus or immunization with WCV, we have previously shown that CD4 + Th17 responses to a number of antigens provide protection against colonization in mice 19 and can be detected in the peripheral blood mononuclear cells of human adults and children. [40][41][42] However, the nature and localization of these protective T m cells have not been previously examined.…”

Differential IL-17A response to S. pneumoniae in adenoid tissue of children with sleep disordered breathing and otitis media with effusion

“…This study elucidates the possible mechanisms associated with OME and pneumococcal carriage. Future novel therapeutics capable of modifying the balance of Th17/T reg function or direct targeting the IL-17A related inflammatory response might be beneficial for children with persistent OME or recurrent AOM requiring repeated ventilation tube insertion 30,31 .…”

Conjugation Mechanism for Pneumococcal Glycoconjugate Vaccines: Classic and Emerging Methods

“…It has been established that CD4+ T helper type 17 (Th17) cell response leads to the reduction of pneumococcal colonization, killing and clearing of pneumococci by recruiting neutrophils to the site of infection. This type of response could reduce pneumococcal colonization, promoting clearance and is independent of CPS type [ 53 , 54 , 55 , 56 , 57 ].…”