Neonatal Deficiencies in NK cell-Activating Cytokines in the Context of Bordetella pertussis Infection

Abstract

Abstract Whooping cough, caused by Bordetella pertussis, has seen a resurgence in recent years, in part due to the switch from the whole cell to acellular vaccine. Although both adults and infants can suffer from severe paroxysmal cough, infants can experience a fatal health decline. Disease progression in infant and adult mouse models show some parallels to human disease. Adult mice exhibit severe lung pathology, but overcome infection, while infant mice experience mild lung pathology, develop leukocytosis, bacterial dissemination, and succumb to infection. We hypothesize that this discrepancy in response to infection is due to a deficiency in neonatal Interferon gamma (IFN-y) production by Natural Killer (NK) cells, which can activate protective T-helper 1 (Th1) cells. We further hypothesize that this deficiency is in part due to the inability of neonatal antigen presenting cells to produce the NK cell-activating cytokines Interleukin (IL) 12 and IL18 when exposed to B. pertussis. To test this hypothesis, we isolated splenocytes from infected and uninfected infant and adult mice, incubated with heat killed B. pertussis, and analyzed for mRNA expression of cytokines via qRT-PCR. While adult splenocytes responded robustly with upregulated expression of IL12 and TNF-α, infant splenocytes failed to upregulate expression of these cytokines in response to bacterial stimulation. Moreover, analysis of lung tissue from infected mice revealed robust upregulation of IL12, IL18 and TNF-α in adult mice but not in infant mice. These results indicate that infant mouse cells fail to upregulate expression of NK cell-activating cytokines in response to B. pertussis infection, leading to a lack of protective IFN-y responses.