Immune stability predicts tuberculosis infection risk in a wild mammal

Immunity is one of the most variable phenotypic traits in animals; however, some individuals may show less fluctuation in immune traits, resulting in stable patterns of immune variation over time. It is currently unknown whether immune variation has consequences for infectious disease risk. In this study, we identified moderately stable immune traits in wild African buffalo and asked whether the stability of these traits affected bovine tuberculosis (TB) infection risk. We found that adaptive immune traits such as the level of IFN-γ released after white blood cell stimulation, the number of circulating lymphocytes, and the level of antibodies against bovine adenovirus-3 were moderately repeatable (i.e. stable) over time, whereas parameters related to innate immunity either had low repeatability (circulating eosinophil numbers) or were not repeatable (e.g. neutrophil numbers, plasma bacteria killing capacity). Intriguingly, individuals with more repeatable IFN-γ and lymphocyte levels were at a significantly higher risk of acquiring TB infection. In stark contrast, average IFN-γ and lymphocyte levels were poor predictors of TB risk, indicating that immune variability rather than absolute response level better captured variation in disease susceptibility. This work highlights the important and under-appreciated role of immune variability as a predictor of infection risk.

免疫是动物表型性状中变异程度最高的类别之一；然而部分个体的免疫性状波动幅度较低，随时间推移呈现出稳定的免疫变异模式。目前学界尚未明确免疫变异是否会对传染病感染风险产生影响。本研究在野生非洲水牛中筛选出中度稳定的免疫性状，并探究此类性状的稳定性是否会影响牛结核（bovine tuberculosis, TB）感染风险。研究发现，适应性免疫相关性状——如白细胞（white blood cell）刺激后释放的干扰素γ（IFN-γ）水平、循环淋巴细胞计数以及抗牛腺病毒3型（bovine adenovirus-3）抗体滴度——随时间推移均呈现中度可重复性（即稳定性）；而与先天免疫相关的参数则要么可重复性较低（循环嗜酸性粒细胞计数），要么完全不可重复（例如中性粒细胞计数、血浆细菌杀伤能力）。值得注意的是，干扰素γ与淋巴细胞水平可重复性更高的个体，其感染牛结核的风险显著更高。与之形成鲜明对比的是，干扰素γ与淋巴细胞的平均水平无法有效预测牛结核感染风险，这表明免疫变异程度而非绝对反应水平，更能反映个体的疾病易感性差异。本研究凸显了免疫变异作为感染风险预测因子的重要性，而这一作用此前未得到足够重视。