Journal article
Infection with Mycobacterium avium subsp. paratuberculosis Results in Rapid Interleukin-1β Release and Macrophage Transepithelial Migration
Infection and immunity, Vol.80(9), pp.3225-3235
09/2012
Handle:
https://hdl.handle.net/2376/105776
PMCID: PMC3418758
PMID: 22778093
Abstract
Pathogen processing by the intestinal epithelium involves a dynamic innate immune response initiated by pathogen-epithelial cell cross talk. Interactions between epithelium and
Mycobacterium avium
subsp.
paratuberculosis
have not been intensively studied, and it is currently unknown how the bacterium-epithelial cell cross talk contributes to the course of infection. We hypothesized that
M. avium
subsp.
paratuberculosis
harnesses host responses to recruit macrophages to the site of infection to ensure its survival and dissemination. We investigated macrophage recruitment in response to
M. avium
subsp.
paratuberculosis
using a MAC-T bovine macrophage coculture system. We show that
M. avium
subsp.
paratuberculosis
infection led to phagosome acidification within bovine epithelial (MAC-T) cells as early as 10 min, which resulted in upregulation of interleukin-1β (IL-1β) at transcript and protein levels. Within 10 min of infection, macrophages were recruited to the apical side of MAC-T cells. Inhibition of phagosome acidification or IL-1β abrogated this response, while MCP-1/CCL-2 blocking had no effect. IL-1β processing was dependent upon Ca
2+
uptake from the extracellular medium and intracellular Ca
2+
oscillations, as determined by EGTA and BAPTA-AM [1,2-bis(2-aminophenoxy) ethane-
N
,
N
,
N
′,
N
′-tetraacetic acid tetrakis (acetoxymethyl ester)] treatments. Thus,
M. avium
subsp.
paratuberculosis
is an opportunist that takes advantage of extracellular Ca
2+
-dependent phagosome acidification and IL-1β processing in order to efficiently transverse the epithelium and enter its niche—the macrophage.
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Details
- Title
- Infection with Mycobacterium avium subsp. paratuberculosis Results in Rapid Interleukin-1β Release and Macrophage Transepithelial Migration
- Creators
- Elise A Lamont - Department of Veterinary Population MedicineScott M O'Grady - Department of Animal Science, University of Minnesota, St. Paul, Minnesota, USAWilliam C Davis - Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington, USATorsten Eckstein - Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USASrinand Sreevatsan - Department of Veterinary Population Medicine
- Publication Details
- Infection and immunity, Vol.80(9), pp.3225-3235
- Academic Unit
- Veterinary Microbiology and Pathology, Department of
- Publisher
- American Society for Microbiology; 1752 N St., N.W., Washington, DC
- Identifiers
- 99900546888301842
- Language
- English
- Resource Type
- Journal article