Dataset Information

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis.

ABSTRACT: The bacterial pathogen Listeria monocytogenes causes foodborne systemic disease in pregnant women, which can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to the placenta and fetus. Host-pathogen interactions in the decidua during this early stage of infection remain poorly understood. Here, we assessed the dynamics of L. monocytogenes infection in primary human decidual organ cultures and in the murine decidua in vivo A high inoculum was necessary to infect both human and mouse deciduas, and the data support the existence of a barrier to initial colonization of the murine decidua. If successful, however, colonization in both species was followed by significant bacterial expansion associated with an inability of the decidua to mount appropriate innate cellular immune responses. The innate immune deficits included the failure of bacterial foci to attract macrophages and NK cells, cell types known to be important for early defenses against L. monocytogenes in the spleen, as well as a decrease in the tissue density of inflammatory Ly6C^hi monocytes in vivo These results suggest that the infectivity of the decidua is not the result of an enhanced recruitment of L. monocytogenes to the gestational uterus but rather is due to compromised local innate cellular immune responses.

SUBMITTER: Rizzuto G

PROVIDER: S-EPMC5520438 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis.

Rizzuto Gabrielle G Tagliani Elisa E Manandhar Priyanka P Erlebacher Adrian A Bakardjiev Anna I AI

Infection and immunity 20170719 8

The bacterial pathogen <i>Listeria monocytogenes</i> causes foodborne systemic disease in pregnant women, which can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to the placenta and fetus. Host-pathogen interactions in the decidua during this early stage of infection remain poorly understood. Here, we assessed the dynamics of <i>L. monocyt ...[more]

PMID: 28507070

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Project description:Over 1.9 billion individuals require preventive chemotherapy through mass drug administration (MDA). Community-directed MDA relies on volunteer community medicine distributors (CMDs) and their achievement of high coverage and compliance. Yet, it is unknown if village social networks influence effective MDA implementation by CMDs. In Mayuge District, Uganda, census-style surveys were conducted for 16,357 individuals from 3,491 households in 17 villages. Praziquantel, albendazole, and ivermectin were administered for one month in community-directed MDA to treat Schistosoma mansoni, hookworm, and lymphatic filariasis. Self-reported treatment outcomes, socioeconomic characteristics, friendship networks, and health advice networks were collected. We investigated systematically missed coverage and noncompliance. Coverage was defined as an eligible person being offered at least one drug by CMDs; compliance included ingesting at least one of the offered drugs. These outcomes were analyzed as a two-stage process using a Heckman selection model. To further assess if MDA through CMDs was working as intended, we examined the probability of accurate drug administration of 1) praziquantel, 2) both albendazole and ivermectin, and 3) all drugs. This analysis was conducted using bivariate Probit regression. Four indicators from each social network were examined: degree, betweenness centrality, closeness centrality, and the presence of a direct connection to CMDs. All models accounted for nested household and village standard errors. CMDs were more likely to offer medicines, and to accurately administer the drugs as trained by the national control programme, to individuals with high friendship degree (many connections) and high friendship closeness centrality (households that were only a short number of steps away from all other households in the network). Though high (88.59%), additional compliance was associated with directly trusting CMDs for health advice. Effective treatment provision requires addressing CMD biases towards influential, well-embedded individuals in friendship networks and utilizing health advice networks to increase village trust in CMDs.

Project description:Adaptive immune system, principally governed by the T cells-dendritic cells (DCs) nexus, is an essential mediator of gestational fetal tolerance and protection against infection. However, the exact composition and dynamics of DCs and T cell subsets in gestational tissues are not well understood. These are controlled in human physiology by a complex interplay of alloantigen distribution and presentation, cellular/humoral active and passive tolerance, hormones/chemokines/angiogenic factors and their gradients, systemic and local microbial communities. Reductive discrimination of these factors in physiology and pathology of model systems and humans requires simplification of the model and increased resolution of interrogative technologies. As a baseline, we have studied the gestational tissue dynamics in the syngeneic C57BL/6 mice, as the simplest immunological environment, and focused on validating the approach to increased data density and computational analysis pipeline afforded by highly polychromatic flow cytometry and machine learning interpretation. We mapped DC and T cell subsets, and comprehensively examined their maternal (decidual)-fetal (placental) interface dynamics. Both frequency and composition of decidual DCs changed across gestation, with a dramatic increase in myeloid DCs in early pregnancy, and exclusion of plasmacytoid DCs. CD4+ T cells, in contrast, were lower at all gestational ages and an unusual CD4-CD8-TCRαβ+group was prominent at mid-pregnancy. Dimensionality reduction with machine learning-aided clustering revealed that CD4-CD8- T cells were phenotypically different from CD4+ and CD8+ T cells. Additionally, divergence between maternal decidual and fetal placental compartment was prominent, with absence of DCs from the placenta, but not decidua or embryo. These results provide a novel framework and a syngeneic baseline on which the specific role of alloantigen/tolerance, polymicrobial environment, and models of pregnancy pathology can be precisely modeled and analyzed.

Dataset Information

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis.

Publications

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis.

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