Division of Immunology, Department of Pathology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.
Parasite Immunol. 2020 Sep;42(9):e12721. doi: 10.1111/pim.12721. Epub 2020 May 3.
Both maternal microbiota and helminth infection may alter offspring immunity but the relationship between these is underexplored. We hypothesized that maternal helminth exposure prior to pregnancy has lasting consequences on offspring intestinal microbiota and consequent immunity. Female BALB/c adult mice were infected with 500L3 Nippostrongylus brasiliensis (N brasiliensis). Infection was cleared by ivermectin treatment, and mice were mated 3 weeks post-infection (NbM). Control mice were not infected but were exposed to ivermectin (NvM). We analysed maternal gut microbiota during pregnancy, breastmilk microbiota and offspring faecal microbiota and immunity 2 weeks after delivery. During pregnancy, NbM (Mothers previously infected with Nippostrongylus brasiliensis) displayed significantly altered stool bacterial communities (R = .242; P = .001), with increased abundance of Enterococcaceae versus NvM (Naive mothers). Similarly, we observed a profound impact on breastmilk microbiota in NbM vs NvM. Moreover, NbM pups showed significantly altered gut microbial communities at 14 days of age versus those born to NvM with increased relative abundance of Coriobacteriaceae and Micrococcaceae. These changes were associated with alterations in pup immunity including increased frequencies and numbers of activated CD4 T cells (CD4 + CD44hi) in NbM offspring spleens. Taken together, we show that preconception helminth infections impact offspring immunity possibly through alteration of maternal and offspring microbiota.
母体微生物群和寄生虫感染都可能改变后代的免疫，但两者之间的关系尚未得到充分探索。我们假设，怀孕前母体寄生虫感染会对后代肠道微生物群产生持久影响，并进而影响免疫。雌性 BALB/c 成年小鼠被感染 500L3 旋毛虫（N 旋毛虫）。用伊维菌素治疗清除感染，感染后 3 周进行交配（NbM）。对照小鼠未感染，但接受伊维菌素处理（NvM）。我们分析了怀孕期母体肠道微生物群、母乳微生物群和后代粪便微生物群以及分娩后 2 周的免疫。在怀孕期间，NbM（先前感染旋毛虫的母亲）粪便细菌群落发生显著改变（R = .242；P = .001），肠球菌科的丰度增加，而 NvM（未感染的母亲）则减少。同样，我们观察到 NbM 与 NvM 相比，母乳微生物群也受到了深刻影响。此外，与 NvM 相比，NbM 幼鼠在 14 天时肠道微生物群落发生显著改变，其相对丰度增加了柯里氏菌科和微球菌科。这些变化与幼鼠免疫的改变有关，包括 NbM 后代脾脏中激活的 CD4 T 细胞（CD4 + CD44hi）的频率和数量增加。总之，我们表明，孕前寄生虫感染可能通过改变母体和后代的微生物群来影响后代的免疫。
