Data values for figures.

Nontyphoidal and enteric fever serovars of Salmonella enterica display distinctive interactions with serum antibodies and the complement system, which initiate the host immune response to invading microbes. This study examines the contributions of lipopolysaccharide O-antigen (O-ag) and the S. Typhi Vi polysaccharide capsule to serum resistance, complement activation and deposition, and immunoglobulin (Ig) binding in nontyphoidal S. enterica serovar Typhimurium and the enteric fever serovars S. Typhi and S. Paratyphi A. Although all three serovars are resistant to serum killing, S. Typhi and S. Paratyphi A exhibit lower levels of Ig binding, complement binding and complement activation compared to S. Typhimurium. In S. Typhimurium, WzzB-dependent long O-antigen (L O-ag) production with 16-to-35 repeating O-ag units, and FepE-dependent very long O-antigen (VL O-ag) production with over 100 repeating O-ag units, are required for serum resistance but do not prevent IgM binding or complement deposition. S. Typhi lacks VL O-ag, but its production of Vi capsule inhibits IgM binding and complement deposition, while acting in concert with L O-ag to resist serum killing. In S. Paratyphi A, L O-ag production is deficient due to a hypofunctional WzzB protein, but this is compensated by greater quantities of VL O-ag, which are required for serum resistance. Restoration of WzzB function by exchange with the S. Typhimurium or S. Typhi wzzB alleles can restore L O-ag production in S. Paratyphi A but decreases VL O-ag production, resulting in increased IgM binding. Replacement of the S. Paratyphi A O2-type polysaccharide with the S. Typhi O9 polysaccharide further increases IgM binding of S. Paratyphi A, which enhances complement activation but not complement deposition. Lastly, a gene duplication of rfbV in S. Paratyphi A is necessary for higher levels of VL O-ag and resistance to complement deposition and antibody binding. Collectively, these observations demonstrate fundamental differences between nontyphoidal and enteric fever Salmonella serovars in their interactions with innate immune effectors. Whereas nontyphoidal S. Typhimurium elicits, exploits and withstands the host acute inflammatory response, the enteric fever serovars S. Typhi and S. Paratyphi A evade it by limiting antibody recognition and complement activation and deposition.肠炎沙门氏菌（Salmonella enterica）的非伤寒型与肠热型血清型，与血清抗体及补体系统呈现独特的相互作用，而补体系统可启动宿主针对入侵微生物的免疫应答。本研究以非伤寒型肠炎沙门氏菌血清型鼠伤寒沙门氏菌（S. Typhimurium）、肠热型血清型伤寒沙门氏菌（S. Typhi）及副伤寒甲沙门氏菌（S. Paratyphi A）为研究对象，探究了脂多糖O抗原（lipopolysaccharide O-antigen，O-ag）与伤寒沙门氏菌Vi多糖荚膜（Vi polysaccharide capsule）对血清抗性、补体激活与沉积、免疫球蛋白（immunoglobulin，Ig）结合的影响。尽管三种血清型均具有血清抗性，但伤寒沙门氏菌与副伤寒甲沙门氏菌的抗体结合、补体结合及补体激活水平均低于鼠伤寒沙门氏菌。在鼠伤寒沙门氏菌中，依赖WzzB合成的长链O抗原（long O-antigen，L O-ag，含16~35个O抗原重复单元）以及依赖FepE合成的超长链O抗原（very long O-antigen，VL O-ag，含100个以上O抗原重复单元）是血清抗性所必需的，但不会阻断IgM结合与补体沉积。伤寒沙门氏菌不具备超长链O抗原，但其产生的Vi荚膜可抑制IgM结合与补体沉积，并与长链O抗原协同发挥血清抗性作用。在副伤寒甲沙门氏菌中，由于WzzB蛋白功能低下，其长链O抗原合成存在缺陷，但该缺陷可通过过量合成的超长链O抗原得到补偿，而后者正是血清抗性所必需的。通过替换鼠伤寒沙门氏菌或伤寒沙门氏菌的wzzB等位基因以恢复WzzB功能，可修复副伤寒甲沙门氏菌的长链O抗原合成，但会降低其超长链O抗原的产量，进而导致IgM结合水平升高。用伤寒沙门氏菌的O9多糖替换副伤寒甲沙门氏菌的O2型多糖，可进一步提升其IgM结合水平，该变化会增强补体激活，但不会影响补体沉积。最后，副伤寒甲沙门氏菌中rfbV基因的重复是其合成大量超长链O抗原、抵御补体沉积与抗体结合的必要条件。综上，上述研究结果表明，非伤寒型与肠热型沙门氏菌血清型在与先天免疫效应分子的相互作用方面存在根本性差异。非伤寒型的鼠伤寒沙门氏菌可引发、利用并耐受宿主的急性炎症应答，而肠热型的伤寒沙门氏菌与副伤寒甲沙门氏菌则通过限制抗体识别、抑制补体激活与沉积来逃避免疫攻击。