Dubois Violaine, Chatagnon Jonathan, Thiriard Anaïs, Bauderlique-Le Roy Hélène, Debrie Anne-Sophie, Coutte Loïc, Locht Camille
CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR9017-CIIL-Center for Infection and Immunity of Lille, Univ. Lille, 59000, Lille, France.
CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US41-UMS 2014-PLBS, Univ. Lille, 59000, Lille, France.
NPJ Vaccines. 2021 Jan 8;6(1):6. doi: 10.1038/s41541-020-00270-8.
Pertussis has made a spectacular rebound in countries that have switched from whole-cell (wPV) to acellular pertussis vaccines (aPV). Here, we show that, unlike wPV, aPV, while protective against lung colonization by Bordetella pertussis (Bp), did not protect BALB/c mice from nasal colonization, but instead substantially prolonged nasal carriage. aPV prevented the natural induction of nasal interleukin-17 (IL-17)-producing and interferon-γ (IFN-γ)-producing CD103 CD44 CD69 CD4-resident memory T (T) cells. IL-17-deficient, but not IFN-γ-deficient, mice failed to clear nasal Bp, indicating a key role of IL-17 T cells in the control of nasal infection. These cells appeared essential for neutrophil recruitment, crucial for clearance of Bp tightly bound to the nasal epithelium. Transfer of IL-17 T cells from Bp-infected mice to IL-17-deficient mice resulted in neutrophil recruitment and protection against nasal colonization. Thus, aPV may have augmented the Bp reservoir by inhibiting natural T cell induction and neutrophil recruitment, thereby contributing to the pertussis resurgence.
在已从全细胞百日咳疫苗（wPV）转换为无细胞百日咳疫苗（aPV）的国家，百日咳出现了显著反弹。在此，我们表明，与wPV不同，aPV虽然能预防百日咳博德特氏菌（Bp）在肺部的定植，但不能保护BALB/c小鼠免受鼻腔定植，反而显著延长了鼻腔携带时间。aPV阻止了鼻腔中产生白细胞介素-17（IL-17）和干扰素-γ（IFN-γ）的CD103⁺CD44⁺CD69⁺CD4⁺组织驻留记忆T（T）细胞的自然诱导。IL-17缺陷但IFN-γ不缺陷的小鼠无法清除鼻腔中的Bp，这表明IL-17⁺ T细胞在控制鼻腔感染中起关键作用。这些细胞对于中性粒细胞募集似乎至关重要，而中性粒细胞募集对于清除紧密结合在鼻上皮的Bp至关重要。将来自Bp感染小鼠的IL-17⁺ T细胞转移到IL-17缺陷小鼠中可导致中性粒细胞募集并提供针对鼻腔定植的保护。因此，aPV可能通过抑制天然T细胞诱导和中性粒细胞募集增加了Bp储存库，从而导致百日咳的再次流行。
