Wander Katherine, Fujita Masako, Mattison Siobhan M, Duris Margaret, Gauck Megan, Hopt Tessa, Lacy Katherine, Foligno Angela, Ulloa Rebecca, Dodge Connor, Mowo Frida, Kiwelu Ireen, Mmbaga Blandina T
Department of Anthropology, Binghamton University (SUNY), Binghamton, NY, USA.
Department of Anthropology, Michigan State University, East Lansing, MI, USA.
Evol Med Public Health. 2022 Jun 13;10(1):295-304. doi: 10.1093/emph/eoac020. eCollection 2022.
The human immune system has evolved to balance protection against infection with control of immune-mediated damage and tolerance of commensal microbes. Such tradeoffs between protection and harm almost certainly extend to the immune system of milk.
Among breastfeeding mother-infant dyads in Kilimanjaro, Tanzania, we characterized proinflammatory milk immune responses to (an infectious agent) and (a benign target) as the increase in interleukin-6 after 24 h of incubation with each bacterium. We characterized incident infectious diseases among infants through passive monitoring. We used Cox proportional hazards models to describe associations between milk immune activity and infant infectious disease.
Among infants, risk for respiratory infections declined with increasing milk proinflammatory response to (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.54, 0.86; : 0.001), while risk for gastrointestinal infections increased with increasing milk proinflammatory response to (HR: 1.44; 95% CI: 1.05, 1.99; : 0.022). Milk proinflammatory responses to and were positively correlated (Spearman's rho: 0.60; : 0.000).
These findings demonstrate a tradeoff in milk immune activity: the benefits of appropriate proinflammatory activity come at the hazard of misdirected proinflammatory activity. This tradeoff is likely to affect infant health in complex ways, depending on prevailing infectious disease conditions. How mother-infant dyads optimize proinflammatory milk immune activity should be a central question in future ecological-evolutionary studies of the immune system of milk.
人类免疫系统已经进化到在抵御感染与控制免疫介导的损伤以及对共生微生物的耐受性之间取得平衡。这种保护与伤害之间的权衡几乎肯定也适用于乳汁中的免疫系统。
在坦桑尼亚乞力马扎罗的母乳喂养母婴对中，我们将乳汁对（一种感染因子）和（一个良性靶点）的促炎免疫反应表征为与每种细菌孵育24小时后白细胞介素-6的增加。我们通过被动监测来确定婴儿中发生的传染病。我们使用Cox比例风险模型来描述乳汁免疫活性与婴儿传染病之间的关联。
在婴儿中，随着乳汁对的促炎反应增加，呼吸道感染风险下降（风险比[HR]：0.68；95%置信区间[CI]：0.54，0.86；P：0.001），而随着乳汁对的促炎反应增加，胃肠道感染风险增加（HR：1.44；95%CI：1.05，1.99；P：0.022）。乳汁对和的促炎反应呈正相关（斯皮尔曼相关系数：0.60；P：0.000）。
这些发现表明乳汁免疫活性存在一种权衡：适当促炎活性的益处伴随着促炎活性方向错误的风险。这种权衡可能会以复杂的方式影响婴儿健康，具体取决于当时的传染病状况。母婴对如何优化乳汁促炎免疫活性应该是未来乳汁免疫系统生态进化研究的核心问题。
