Selenoprotein expression in macrophages is critical for optimal clearance of parasitic helminth Nippostrongylus brasiliensis

Shakira M. Nelson, Ashley E. Shay, Jamaal L. James, Bradley A. Carlson, Joseph F. Urban, K. Sandeep Prabhu

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The plasticity of macrophages is evident in helminthic parasite infections, providing protection from inflammation. Previously we demonstrated that the micronutrient selenium induces a phenotypic switch in macrophage activation from a classically activated (pro-inflammatory; M1/CAM) toward an alternatively activated (anti-inflammatory; M2/AAM) phenotype, where cyclooxygenase (COX)-dependent cyclopentenone prostaglandin J2 (15d-PGJ2) plays a key role. Here, we hypothesize that dietary selenium modulates macrophage polarization toward an AAM phenotype to assist in the increasing clearance of adult Nippostrongylus brasiliensis, a gastrointestinal nematode parasite. Mice on a selenium-adequate (0.08 ppm) diet significantly augmented intestinal AAM presence while decreasing adult worms and fecal egg production when compared with infection of mice on selenium-deficient (<0.01 ppm) diet. Further increase in dietary selenium to supraphysiological levels (0.4 ppm) had very little or no impact on worm expulsion. Normal adult worm clearance and enhanced AAM marker expression were observed in the selenium-supplemented Trspfl/flCreWT mice that express selenoproteins driven by tRNASec (Trsp), whereas N. brasiliensis-infected Trspfl/flCreLysM selenium-supplemented mice showed a decreased clearance, with lowered intestinal expression of several AAM markers. Inhibition of the COX pathway with indomethacin resulted in delayed worm expulsion in selenium-adequate mice. This was rescued with 15d-PGJ2, which partially recapitulated the effect of selenium supplementation on fecal egg output in addition to increasing markers of AAMs in the small intestine. Antagonism of PPARγ blocked the effect of selenium. These results suggest that optimal expression of selenoproteins and selenium-dependent production of COX-derived endogenous prostanoids, such as Δ12- PGJ2 and 15d-PGJ2, may regulate AAM activation to enhance anti-helminthic parasite responses.

Original languageEnglish (US)
Pages (from-to)2787-2798
Number of pages12
JournalJournal of Biological Chemistry
Volume291
Issue number6
DOIs
StatePublished - Feb 5 2016

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Nippostrongylus
Selenoproteins
Macrophages
Helminths
Selenium
Prostaglandin-Endoperoxide Synthases
Nutrition
Ovum
Parasites
Chemical activation
Diet
Phenotype
Parasitic Diseases
Peroxisome Proliferator-Activated Receptors
Macrophage Activation
Micronutrients
Computer aided manufacturing
Indomethacin
Small Intestine
Prostaglandins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Nelson, Shakira M. ; Shay, Ashley E. ; James, Jamaal L. ; Carlson, Bradley A. ; Urban, Joseph F. ; Prabhu, K. Sandeep. / Selenoprotein expression in macrophages is critical for optimal clearance of parasitic helminth Nippostrongylus brasiliensis. In: Journal of Biological Chemistry. 2016 ; Vol. 291, No. 6. pp. 2787-2798.
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Selenoprotein expression in macrophages is critical for optimal clearance of parasitic helminth Nippostrongylus brasiliensis. / Nelson, Shakira M.; Shay, Ashley E.; James, Jamaal L.; Carlson, Bradley A.; Urban, Joseph F.; Prabhu, K. Sandeep.

In: Journal of Biological Chemistry, Vol. 291, No. 6, 05.02.2016, p. 2787-2798.

Research output: Contribution to journalArticle

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T1 - Selenoprotein expression in macrophages is critical for optimal clearance of parasitic helminth Nippostrongylus brasiliensis

AU - Nelson, Shakira M.

AU - Shay, Ashley E.

AU - James, Jamaal L.

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AU - Urban, Joseph F.

AU - Prabhu, K. Sandeep

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