| First Author | Martens GW | Year | 2012 |
| Journal | J Leukoc Biol | Volume | 91 |
| Issue | 6 | Pages | 849-57 |
| PubMed ID | 22227965 | Mgi Jnum | J:184951 |
| Mgi Id | MGI:5426770 | Doi | 10.1189/jlb.0311164 |
| Citation | Martens GW, et al. (2012) Hypercholesterolemic LDL receptor-deficient mice mount a neutrophilic response to tuberculosis despite the timely expression of protective immunity. J Leukoc Biol 91(6):849-57 |
| abstractText | The prevalence of hypercholesterolemia is rising in industrialized and developing countries. We reported previously that host defense against Mtb was impaired by hypercholesterolemia in ApoE(-/-) mice, raising the possibility that people with HC could be more vulnerable to TB. The present study examined whether TB immunity was similarly impaired in a different hypercholesterolemic model, LDL-R(-/-) mice, which developed comparable elevation of total serum cholesterol as ApoE(-/-)mice when fed HC or LC diets. Like ApoE(-/-) mice, LDL-R(-/-) mice had an exaggerated lung inflammatory response to Mtb with increased tissue necrosis. Inflammation, foamy macrophage formation, and tissue necrosis in LDL-R(-/-) mice increased with the degree of hypercholesterolemia. Unlike ApoE(-/-) mice, LDL-R(-/-) mice fed a HC diet mounted a timely and protective adaptive immune response that restricted mycobacterial replication comparably with WT mice. Thus, ApoE(-/-) and LDL-R(-/-) mice share a cholesterol-dependent hyperinflammatory TB phenotype but do not share the impairment of adaptive immunity found in ApoE(-/-) mice. The impact of hypercholesterolemia on TB immunity is more complex than appreciated by total cholesterol alone, possibly reflecting the different functional effect of specific lipoprotein particles. |
