Dataset Information

Mycobacterium avium Subspecies paratuberculosis Infects and Replicates within Human Monocyte-Derived Dendritic Cells.

ABSTRACT: BACKGROUND:Mycobacterium avium subspecies paratuberculosis (MAP), a member of the mycobacteriaceae family, causes Johne's disease in ruminants, which resembles Crohn's disease (CD) in humans. MAP was proposed to be one of the causes of human CD, but the evidence remains elusive. Macrophages were reported to be the only cell where MAP proliferates in ruminants and humans and is likely the major producer of TNF?-associated inflammation. However, whether human dendritic cells (DCs), another major antigen-presenting cell (APC), have the ability to harbor MAP and disseminate infection, remains unknown. METHODS:Human monocyte-derived dendritic cells (moDCs) were infected with MAP and phagocytosis and intracellular survival were quantified by immunofluorescence (IF) and colony counts, respectively. MoDC cytokine expression was measured via ELISA and their activation state was measured via flow cytometry. RESULTS:We showed that MAP can infect and replicate in human moDCs as means to evade the immune system for successful infection, through inhibition of the phago-lysosome fusion via the secretion of protein tyrosine phosphatase PtpA. This mechanism initially led to a state of tolerance in moDCs and then subsequently caused a pro-inflammatory response as infection persisted, characterized by the upregulation of IL-6 and TNF?, and downregulation of IL-10. Moreover, we showed that moDCs have the ability to phagocytose up to 18% of MAP, when exposed at a multiplicity of infection of 1:1. CONCLUSION:Infection and subsequent proliferation of MAP within moDCs could provide a unique means for the dissemination of MAP to lymphoid tissue, while altering immune responses to facilitate the persistence of infection of host tissues in CD.

SUBMITTER: Rees WD

PROVIDER: S-EPMC7409171 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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<i>Mycobacterium avium</i> Subspecies <i>paratuberculosis</i> Infects and Replicates within Human Monocyte-Derived Dendritic Cells.

Rees William D WD Lorenzo-Leal Ana C AC Steiner Theodore S TS Bach Horacio H

Microorganisms 20200703 7

<h4>Background</h4><i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> (MAP), a member of the mycobacteriaceae family, causes Johne's disease in ruminants, which resembles Crohn's disease (CD) in humans. MAP was proposed to be one of the causes of human CD, but the evidence remains elusive. Macrophages were reported to be the only cell where MAP proliferates in ruminants and humans and is likely the major producer of TNFα-associated inflammation. However, whether human dendritic cells ...[more]

PMID: 32635236

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Project description:During early Mycobacterium avium subspecies paratuberculosis (Map) infection, complex interactions occur between the bacteria, cells from the mononuclear phagocyte system (MPS) including both resident (macrophages and dendritic cells) and recruited (monocytes) cells, and other mucosal sentinel cells such as ?? T lymphocytes. Though the details of early host-pathogen interactions in cattle remain largely underexplored, our hypothesis is that these significantly influence development of host immunity and ultimate success or failure of the host to respond to Map infection. The aims of the present study were to first characterize monocyte-derived MPS cells from young calves with respect to their immunophenotype and function. Then, we set out to investigate the effects of WC1+ and WC1neg ?? T lymphocytes on (1) the differentiation of autologous monocytes and (2) the maturation of autologous monocyte-derived dendritic cells (MDDCs). To achieve this, peripheral blood WC1+ or WC1neg ?? T lymphocytes were cocultured with either autologous freshly isolated peripheral blood-derived monocytes or autologous immature MDDCs (iMDDCs). We began by measuring several markers of interest on MPS cells. Useful markers to distinguish monocyte-derived macrophages (MDMs) from MDDCs include CD11b, CD163, and CD172a, which are expressed significantly higher on MDMs compared with MDDCs. Function, but not phenotype, was influenced by WC1neg ?? T lymphocytes: viability of Map harvested from monocytes differentiated in the presence of WC1neg ?? T lymphocytes (dMonWC1neg) was significantly lower compared to MDMs and MDDCs. With respect to DC maturation, we first showed that mature MDDCs (mMDDCs) have significantly higher expression of CD11c, CD80, and CD86 compared with iMDDCs, and the phagocytic capacity of mMDDCs is significantly reduced compared to iMDDCs. We then showed that ?? T lymphocyte subsets induce functional (reduced phagocytosis) but not phenotypic (surface marker expression) iMDDC maturation. These data collectively show that ?? T lymphocytes influence differentiation, maturation, and ultimately the function of monocytes during Map infection, which has significant implications on survival of Map and success of host defense during early Map infection.

Dataset Information

Mycobacterium avium Subspecies paratuberculosis Infects and Replicates within Human Monocyte-Derived Dendritic Cells.

Publications

<i>Mycobacterium avium</i> Subspecies <i>paratuberculosis</i> Infects and Replicates within Human Monocyte-Derived Dendritic Cells.

Similar Datasets

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