Immune Modulation by Rural Exposures and Allergy Protection

To determine immune mechanisms that mediate protection against development of allergic disease in rural environments.This study included 146 children from China: 79 from Hong Kong and 67 from the rural county of Conghua. Of the rural children, 30 had been exposed to domestic poultry (DP) at home (DP+) and 37 had not been exposed (DP-).Peripheral blood mononuclear cells were isolated, and secreted T cell signature cytokines were measured (1) at baseline without stimulation and (2) after stimulation with lipopolysaccharides. Gene expression of immune markers related to TH1, TH2, TH17, and regulatory T cells was assessed. Utilizing a murine model of allergic asthma, bioactivity of DP dust extract was examined by looking at ability to induce pulmonary γδT cells involved in early immunologic response. Airway hyperresponsiveness, cellularity from bronchoalveolar lavage aspirate, and cytokine mRNA expression were also evaluated in this murine model.At baseline, rural children showed down-regulated expression of immune-related genes. DP + children had lower baseline mRNA levels of proinflammatory cytokines, including IL1-B and CTL4, and lower innate gene expression when compared with DP- and urban children. Rural children also had lower percentage of eosinophils, associated with allergic inflammation, compared with urban children. Despite down-regulated immune responses at baseline, the ability to mount a robust cytokine response with stimulation from potent innate microbial triggers was preserved in rural children. Specifically, when receiving stimulation with lipopolysaccharides, there was an increase in IFN-y and other proinflammatory cytokines, with production of higher levels in DP+ children compared with DP- and urban children. To examine underlying mechanisms of DP protection from asthma development, the authors conducted experiments in a murine allergic asthma model. Mice were treated with DP dust extracts from a rural environment. Compared with controls, mice treated with DP dust had decreased airway hyperresponsiveness, decreased TH2 allergic response, and had a higher IL-17 expression, which is known to play an immunoregulatory role in the TH2 allergic response.Exposure to a rural environment, especially exposure to DP, is protective against development of allergic disease, including asthma, and was shown to downregulate immune-related genes at baseline and decrease allergic inflammation in the airways. Despite down-regulated baseline immune responses, rural children had preserved capacity to mount immune responses to infectious stimuli. Further, when looking at immune changes more closely in regard to DP exposure, it is evident that immune responses in DP- children are intermediate to those of DP+ and urban children. The fact that DP- children still demonstrate a protective effect compared with urban children suggests that factors other than DP exposure, such as agricultural farming, may also contribute to protective immune responses seen in rural environments.This study adds insight into possible underlying mechanisms through which childhood exposure to rural environments and associated diverse microbiota drive early modulation of immune responses and prevent development of allergic disease. This evolution in understanding is important for primary care providers and indicates novel avenues and future targets for primary prevention of allergic disease.