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Accessibility of O Antigens Shared between Salmonella Serovars Determines Antibody-Mediated Cross-Protection
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-15 , DOI: 10.4049/jimmunol.1900624
Anees Ahmed 1 , Ajay Suresh Akhade 1 , Ayub Qadri 2
Affiliation  

Key Points A large proportion of immunity-relevant anti-Salmonella Abs bind O Ags. Accessibility of shared O Ags is critical for cross-protection with Abs. O Ags of Salmonella may be involved in host–pathogen interaction. Pathogenic Salmonella serovars produce clinical manifestations ranging from systemic infection typhoid to invasive nontyphoidal Salmonella disease in humans. These serovars share a high degree of homology at the genome and the proteome level. However, whether infection or immunization with one serovar provides protection against other serovars has not been well studied. We show in this study that immunization of mice with live typhoidal serovar, Salmonella Typhi, generates cross-reactive immune responses, which provide far greater resistance against challenge with nontyphoidal serovar Salmonella Enteritidis than with another nontyphoidal serovar, Salmonella Typhimurium. Splenic T cells from these immunized mice produced similar levels of IL-2 and IFN-γ upon ex vivo stimulation with Ags prepared from S. Enteritidis and S. Typhimurium. In contrast, Abs against S. Typhi interacted with live intact S. Enteritidis but did not bind intact S. Typhimurium. These pathogen-reactive Abs were largely directed against oligosaccharide (O)-antigenic determinant of LPS that S. Typhi shares with S. Enteritidis. Abs against the O determinant, which S. Typhi shares with S. Typhimurium, were present in the sera of immunized mice but did not bind live intact Salmonella because of surface inaccessibility of this determinant. Similar accessibility-regulated interaction was seen with Abs generated against S. Typhimurium and S. Enteritidis. Our results suggest that the ability of protective Abs elicited with one Salmonella serovar to engage with and consequently provide protection against another Salmonella serovar is determined by the accessibility of shared O Ags. These findings have significant and broader implications for immunity and vaccine development against pathogenic Salmonellae.

中文翻译:

沙门氏菌血清型之间共享的 O 抗原的可及性决定了抗体介导的交叉保护

要点 大部分与免疫相关的抗沙门氏菌抗体结合 O Ags。共享 O Ags 的可访问性对于与 Abs 的交叉保护至关重要。O 沙门氏菌的抗原可能参与宿主-病原体相互作用。致病性沙门氏菌血清型产生的临床表现范围从全身感染伤寒到人类侵袭性非伤寒沙门氏菌病。这些血清型在基因组和蛋白质组水平上具有高度的同源性。然而,用一种血清型感染或免疫是否能提供针对其他血清型的保护尚未得到很好的研究。我们在这项研究中表明,用活伤寒血清型伤寒沙门氏菌免疫小鼠会产生交叉反应性免疫反应,与另一种非伤寒血清型鼠伤寒沙门氏菌相比,它们对非伤寒血清型肠炎沙门氏菌的攻击提供了更大的抵抗力。在用从肠炎沙门氏菌和鼠伤寒沙门氏菌制备的 Ags 进行离体刺激后,来自这些免疫小鼠的脾脏 T 细胞产生相似水平的 IL-2 和 IFN-γ。相比之下,抗伤寒沙门氏菌的抗体与完整的活肠炎沙门氏菌相互作用,但不结合完整的鼠伤寒沙门氏菌。这些病原体反应性抗体主要针对伤寒沙门氏菌与肠炎沙门氏菌共享的 LPS 的寡糖 (O) 抗原决定簇。针对 O 决定簇的抗体,伤寒沙门氏菌与鼠伤寒沙门氏菌共享,存在于免疫小鼠的血清中,但由于该决定簇的表面不可接近性,因此不结合活的完整沙门氏菌。在针对鼠伤寒沙门氏菌和肠炎沙门氏菌产生的抗体中观察到类似的可访问性调节相互作用。我们的结果表明,由一种沙门氏菌血清型引起的保护性抗体与另一种沙门氏菌血清型结合并因此提供保护的能力取决于共享 O Ags 的可及性。这些发现对针对致病性沙门氏菌的免疫和疫苗开发具有重要和更广泛的意义。
更新日期:2020-06-15
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