Crucial role of the central leptin receptor in murine Trypanosoma cruzi (Brazil strain) infection - PubMed (original) (raw)

. 2010 Oct 1;202(7):1104-13.

doi: 10.1086/656189.

Dazhi Zhao, Fabiana S Machado, Louis M Weiss, Gary J Schwartz, Mahalia S Desruisseaux, Yang Zhao, Stephen M Factor, Huan Huang, Chris Albanese, Mauro M Teixeira, Philipp E Scherer, Streamson C Chua Jr, Herbert B Tanowitz

Affiliations

Crucial role of the central leptin receptor in murine Trypanosoma cruzi (Brazil strain) infection

Fnu Nagajyothi et al. J Infect Dis. 2010.

Abstract

Mice carrying a defective leptin receptor gene (db/db mice) are metabolically challenged and upon infection with Trypanosoma cruzi (Brazil strain) suffer high mortality. In genetically modified db/db mice, (NSE-Rb db/db mice), central leptin signaling is reconstituted only in the brain, which is sufficient to correct the metabolic defects. NSE-Rb db/db mice were infected with T. cruzi to determine the impact of the lack of leptin signaling on infection in the absence of metabolic dysregulation. Parasitemia levels, mortality rates, and tissue parasitism were statistically significantly increased in infected db/db mice compared with those in infected NSE-Rb db/db and FVB wild-type mice. There was a reduction in fat mass and blood glucose level in infected db/db mice. Plasma levels of several cytokines and chemokines were statistically significantly increased in infected db/db mice compared with those in infected FVB and NSE-Rb db/db mice. These findings suggest that leptin resistance in individuals with obesity and diabetes mellitus may have adverse consequences in T. cruzi infection.

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Conflict of interest statement

Authors have no commercial or financial interest or conflict of interest

Figures

Figure 1

Figure 1

A. Parasitemia in mice infected with T. cruzi (Brazil strain) (n=5 for each group). 1B: Mortality in mice infected with T. cruzi (Brazil strain). Beginning with 18 days post infection there was a significant (* p<0.05) increase in peripheral parasitemia in infected db/db mice and a 100% mortality compared with NSE-RB db/db and FVB mice (top line).

Figure 2

Figure 2

Representative myocardial histopathology in mice infected with T. cruzi (Brazil strain). Top panels are all low power (10X) and bottom panels are all high power (20x). db/db (LEPR-B null mice), NSE-Rb db/db and FVB mice. Note the increase parasite load and inflammation in the infected db/db mice. Arrows point to pseudocysts which contain T. cruzi amastigotes.

Figure 3

Figure 3

A: Blood glucose determinations in mice infected with T. cruzi (Brazil strain) (n=5 for each group) over 27 days post-infection. There was a significant reduction (p<0.05) in blood glucose concentration in infected db/db mice beginning at day 15 post infection. In the FVB and NSE-RB db/db mice the reduction in blood glucose was significant at day 22 post-infection compared to day zero**. B:** Adiponectin levels in mice infected with T. cruzi (Brazil strain) (n=5 for each group). There was a significant reduction (p<0.05) in adiponectin levels in all 3 groups compared to day zero. Note that in the db/db mice, there was a significant reduction in adiponectin prior to infection.

Figure 4

Figure 4

Plasma cytokine levels in mice infected with T. cruzi (Brazil strain) (n=5 for each group) over 27 days post-infection. There was a significant (*p<0.05) increase in IL-6 and TNF-α in infected db/db mice compared with FVB and NSE-RB db/db mice. The levels of IFN-γ were increased in all three groups but were significantly increased (*p<0.05) in db/db mice compared with FVB and transgenic only at day 24 post infection.

Figure 5

Figure 5

Plasma chemokine levels in mice infected with T. cruzi (Brazil strain) (n=5 for each group) over 27 days post-infection. Levels of CCL-2, CCL-3 and CCl-5 were significantly (*p<0.05) increased in infected db/db mice. CXCL-10 levels were significantly (*p<0.05) increased in infected db/db and NSE-RB db/db mice.

Figure 6

Figure 6

Determination of macrophages by qPCR analysis of F4/80 in white adipose tissue obtained from mice infected with T. cruzi (Brazil strain) 15 days post infection. The baseline values for db/db mice are elevated and infection does not results in an increase over base-line. (n=5 for each group). There was a significant increase (*p<0.05) in levels of F480 in infected NSE-RB db/db and FVB mice.

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