Whipworm Infection Promotes Bacterial Invasion, Intestinal Microbiota Imbalance, and Cellular Immunomodulation.

Infections with Trichuris trichiura are among the most common causes of intestinal parasitism in children worldwide, and the diagnosis is based on microscopic egg identification in the chronic phase of the infection. During parasitism, the adult worm of the trichurid nematode maintains its anterior region inserted in the intestinal mucosa, which causes serious damage and which may open access for gut microorganisms through the intestinal tissue. The immune-regulatory processes taking place during the evolution of the chronic infection are still not completely understood. By use of the Swiss Webster outbred mouse model, mice were infected with 200 eggs, and tolerance to the establishment of a chronic Trichuris muris infection was induced by the administration of a short pulse of dexamethasone during nematode early larval development. The infected mice presented weight loss, anemia, an imbalance of the microbiota, and intense immunological cell infiltration in the large intestine. It was found that mice have a mixed Th1/Th2/Th17 response, with differences being found among the different anatomical locations. After 45 days of infection, the parasitism induced changes in the microbiota composition and bacterial invasion of the large intestine epithelium. In addition, we describe that the excretory-secretory products from the nematode have anti-inflammatory effects on mouse macrophages cultured in vitro, suggesting that T. muris may modulate the immune response at the site of insertion of the worm inside mouse tissue. The data presented in this study suggest that the host immune state at 45 days postinfection with T. muris during the chronic phase of infection is the result of factors derived from the worm as well as alterations to the microbiota and bacterial invasion. Taken together, these results provide new information about the parasite-host-microbiota relationship and open new treatment possibilities.

Expression of purinergic receptors and modulation of P2X7 function by the inflammatory cytokine IFNgamma in human epithelial cells.

The cervical epithelial cell line, HeLa, is one of the oldest and most commonly used cell lines in cell biology laboratories. Although a truncated P2X(7) receptor has recently been identified in HeLa cells, the expression of other purinergic receptors or the function of the P2X(7) protein has not been characterized. We here show that HeLa cells express transcripts for most P2X and P2Y purinergic receptors. Treatment of cells with ATP or other P2X(7) agonists does not stimulate cell death, but can induce atypical calcium fluxes and ion currents. Cervical epithelial cells represent an important target for sexually-transmitted pathogens and are commonly exposed to pro-inflammatory cytokines such as IFNgamma. Stimulation of HeLa cells with IFNgamma upregulates expression of P2X(7) mRNA and full-length protein, modifies ATP-dependent calcium fluxes, and renders the cells sensitive to ATP-induced apoptosis, which can be blocked by a P2X(7) antagonist. IFNgamma treatment also increased dramatically the sensitivity of the intestinal epithelial cell line, HCT8, to ATP-induced apoptosis. Significantly, IFNgamma also stimulated P2X(7) expression on human intestinal tissues. Responses to other purinergic receptor ligands suggest that HeLa cells may also express functional P2Y(1), P2Y(2) and P2Y(6) receptors, which could be relevant for modulating ion homeostasis in the cells.