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fimmu-09-02580 Front Immunology Schistosomiasis athero-protection.pdf (2.58 MB)

Schistosoma mansoni Infection-Induced Transcriptional Changes in Hepatic Macrophage Metabolism Correlate With an Athero-Protective Phenotype

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journal contribution
posted on 2019-03-18, 16:25 authored by Diana Cortes-Selva, Andrew F. Elvington, Andrew Ready, Bartek Rajwa, Edward J. Pearce, Gwendalyn J. Randolph, Keke C. Fairfax

Hepatic macrophages play an essential role in the granulomatous response to infection

with the parasitic helminth Schistosoma mansoni , but the transcriptional changes

that underlie this effect are poorly understood. To explore this, we sorted the two

previously recognized hepatic macrophage populations (perivascular and Kupffer cells)

from naïve and S. mansoni -infected male mice and performed microarray analysis as

part of the Immunological Genome Project. The two hepatic macrophage populations

exhibited remarkably different genomic profiles. However, this diversity was substantially

reduced following infection with S. mansoni , and in fact, both populations demonstrated

increases in transcripts of the monocyte lineage, suggesting that both populations

may be replenished by monocytes following infection. Pathway analysis showed a

profound alteration in global metabolic pathways, including changes to phospholipid

and cholesterol metabolism, as well as amino acid biosynthesis and glucagon

signaling. These changes suggest a possible mechanism for the previously reported

athero-protective effects of S. mansoni infection. Indeed, we find that male ApoE null

mice fed a high-fat diet in combination with S. mansoni infection have reduced plaque

area and increased glucose tolerance as compared to control mice. Transcript analysis

of infected and control high-fat diet fed ApoE−/− mice confirm that ApoC1 , Psat1 ,

and Gys1 are all altered by infection, suggesting that altered hepatic macrophage

metabolism is associated with S. mansoni - induced protection from hyperlipidemia,

atherosclerosis, and glucose intolerance. These results suggest a previously unknown

and unreported role of hepatic macrophages in the modulation of whole body lipid and

glucose metabolism during infection and provide a template for examining the role of immunomodulation on the long-term metabolism of the host.


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