Immunological Signatures after Bordetella pertussis Infection Demonstrate Importance of Pulmonary Innate Immune Cells

Abstract

Effective immunity against Bordetella pertussis is currently under discussion following the stacking evidence of pertussis resurgence in the vaccinated population. Natural immunity is more effective than vaccine-induced immunity indicating that knowledge on infection-induced responses may contribute to improve vaccination strategies. We applied a systems biology approach comprising microarray, flow cytometry and multiplex immunoassays to unravel the molecular and cellular signatures in unprotected mice and protected mice with infection-induced immunity, around a B. pertussis challenge. Pre-existing systemic memory Th1/Th17 cells, memory B-cells, and mucosal IgA specific for Ptx, Vag8, Fim2/3 were detected in the protected mice 56 days after an experimental infection. In addition, pre-existing high activity and reactivation of pulmonary innate cells such as alveolar macrophages, M-cells and goblet cells was detected. The pro-inflammatory responses in the lungs and serum, and neutrophil recruitment in the spleen upon an infectious challenge of unprotected mice were absent in protected mice. Instead, fast pulmonary immune responses in protected mice led to efficient bacterial clearance and harbored potential new gene markers that contribute to immunity against B. pertussis. These responses comprised of innate makers, such as Clca3, Retlna, Glycam1, Gp2, and Umod, next to adaptive markers, such as CCR6+ B-cells, CCR6+ Th17 cells and CXCR6+ T-cells as demonstrated by transcriptome analysis. In conclusion, besides effective Th1/Th17 and mucosal IgA responses, the primary infection-induced immunity benefits from activation of pulmonary resident innate immune cells, achieved by local pathogen-recognition. These molecular signatures of primary infection-induced immunity provided potential markers to improve vaccine-induced immunity against B. pertussis.

T Cell Metabolism Is Dependent on Anatomical Location within the Lung

“…For example, given the differences in the rates of clearance of Ftt and B. pertussis, the flavor and complexity of in vivo activation of T cells is likely to profoundly impact the function of IV 2 T cells. For example, B. pertussis elicits a greater inflammatory response soon postinfection, whereas Ftt fails to trigger detectable inflammation for up to 3 d after inoculation (16,17). Therefore, although ex vivo stimulation results in minor changes in the metabolic profile of IV 2 CD4 + T eff independent of the vaccinating bacterium, our data suggest that the nature of secondary infection may contribute to the overall efficacy of the resident T cell response.…”

Molecular and cellular signatures underlying superior immunity against Bordetella pertussis upon pulmonary vaccination

“…11 This response is comparable to the response induced by a B. pertussis infection, but importantly lacks the mucosal immune responses. 8,[12][13][14] Vaccine administration directly into the respiratory tract provides better protection, compared with intramuscular administration, because of its induction of local immune responses. [15][16][17][18] Protection against B. pertussis challenge has been achieved with various intranasal pertussis vaccine candidates.…”

IL-17-dependent SIgA-mediated protection against nasal Bordetella pertussis infection by live attenuated BPZE1 vaccine

“…28 However, more recently, Raeven et al 29 have shown that pulmonary immunization with pertussis outer membrane vesicles induced superior protection than subcutaneous immunization and this was related to mucosal IgA and Th17 cell induction. The same authors have shown that mucosal IgA and Th1/Th17 cells are also induced by experimental infection of mice with virulent B. pertussis, 30 and Th1/Th17 cells have been demonstrated to be crucial for protection induced by infection. 31 Furthermore, Wilk et al 23 and Misiak et al 32 have reported that infection with virulent B. pertussis induces tissue-resident IL-17-producing CD4 and γδ T cells in the lungs of mice.…”