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Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet-induced obesity

View Article: PubMed Central - PubMed

ABSTRACT

Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high-fat diet-induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil- and macrophage-based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi-infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high-fat diet, toll-like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow-derived macrophages from obese, B. burgdorferi-infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice.

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Increased Lyme carditis severity in diet-induced obesity (DIO). (a) Mean ± standard error of the mean (SEM) carditis (inflammation) scores, calculated as described in experimental procedures by measuring mean numbers of nuclei/region of interest in heart sections from mice infected with indicated bacterial strains, and age-, sex-, and strain-matched mock-infected mice (−Bb). Global values (−Bb and +Bb) are means for all sexes and bacterial strains combined. Representative histology images are provided in Figure S3. (b) Median Borrelia burgdorferi DNA copy number in hearts for indicated mouse strains and sexes and bacterial strains, and all groups (ALL). Each data point corresponds to the copy number values for one mouse. For a and b, values above datasets indicate significant fold-differences for high-fat diet (HFD) versus normal diet (ND) groups. N ≥ 9 mice/diet group for individual experiments. * indicates p < 0.05 HFD versus ND. † indicates p < 0.05 versus age-, sex-, and diet-matched mock-infected control group († symbols placed above and below mean values for each infected diet group)
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Figure 2: Increased Lyme carditis severity in diet-induced obesity (DIO). (a) Mean ± standard error of the mean (SEM) carditis (inflammation) scores, calculated as described in experimental procedures by measuring mean numbers of nuclei/region of interest in heart sections from mice infected with indicated bacterial strains, and age-, sex-, and strain-matched mock-infected mice (−Bb). Global values (−Bb and +Bb) are means for all sexes and bacterial strains combined. Representative histology images are provided in Figure S3. (b) Median Borrelia burgdorferi DNA copy number in hearts for indicated mouse strains and sexes and bacterial strains, and all groups (ALL). Each data point corresponds to the copy number values for one mouse. For a and b, values above datasets indicate significant fold-differences for high-fat diet (HFD) versus normal diet (ND) groups. N ≥ 9 mice/diet group for individual experiments. * indicates p < 0.05 HFD versus ND. † indicates p < 0.05 versus age-, sex-, and diet-matched mock-infected control group († symbols placed above and below mean values for each infected diet group)

Mentions: To determine if DIO affected the pathological outcomes of B. burgdorferi infection, we evaluated inflammation in tibiotarsal joint, heart, brain, and liver. No overt, infection-dependent differences in inflammation were observed in joints, brain, or liver of either ND or HFD mice under multiple experimental conditions (mouse strains, sexes, and bacterial strains), as determined by a murine veterinary pathologist (data not shown). B. burgdorferi-dependent arthritis was presumably not detected in either diet group because animals were considerably older than the optimal age for induction of this pathology in mice (3 weeks) (Barthold et al., 2010). However, inflammation was significantly elevated in the hearts of mice from experimental groups where bacterial DNA burden was increased in DIO (Figure 2).


Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet-induced obesity
Increased Lyme carditis severity in diet-induced obesity (DIO). (a) Mean ± standard error of the mean (SEM) carditis (inflammation) scores, calculated as described in experimental procedures by measuring mean numbers of nuclei/region of interest in heart sections from mice infected with indicated bacterial strains, and age-, sex-, and strain-matched mock-infected mice (−Bb). Global values (−Bb and +Bb) are means for all sexes and bacterial strains combined. Representative histology images are provided in Figure S3. (b) Median Borrelia burgdorferi DNA copy number in hearts for indicated mouse strains and sexes and bacterial strains, and all groups (ALL). Each data point corresponds to the copy number values for one mouse. For a and b, values above datasets indicate significant fold-differences for high-fat diet (HFD) versus normal diet (ND) groups. N ≥ 9 mice/diet group for individual experiments. * indicates p < 0.05 HFD versus ND. † indicates p < 0.05 versus age-, sex-, and diet-matched mock-infected control group († symbols placed above and below mean values for each infected diet group)
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Related In: Results  -  Collection

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Figure 2: Increased Lyme carditis severity in diet-induced obesity (DIO). (a) Mean ± standard error of the mean (SEM) carditis (inflammation) scores, calculated as described in experimental procedures by measuring mean numbers of nuclei/region of interest in heart sections from mice infected with indicated bacterial strains, and age-, sex-, and strain-matched mock-infected mice (−Bb). Global values (−Bb and +Bb) are means for all sexes and bacterial strains combined. Representative histology images are provided in Figure S3. (b) Median Borrelia burgdorferi DNA copy number in hearts for indicated mouse strains and sexes and bacterial strains, and all groups (ALL). Each data point corresponds to the copy number values for one mouse. For a and b, values above datasets indicate significant fold-differences for high-fat diet (HFD) versus normal diet (ND) groups. N ≥ 9 mice/diet group for individual experiments. * indicates p < 0.05 HFD versus ND. † indicates p < 0.05 versus age-, sex-, and diet-matched mock-infected control group († symbols placed above and below mean values for each infected diet group)
Mentions: To determine if DIO affected the pathological outcomes of B. burgdorferi infection, we evaluated inflammation in tibiotarsal joint, heart, brain, and liver. No overt, infection-dependent differences in inflammation were observed in joints, brain, or liver of either ND or HFD mice under multiple experimental conditions (mouse strains, sexes, and bacterial strains), as determined by a murine veterinary pathologist (data not shown). B. burgdorferi-dependent arthritis was presumably not detected in either diet group because animals were considerably older than the optimal age for induction of this pathology in mice (3 weeks) (Barthold et al., 2010). However, inflammation was significantly elevated in the hearts of mice from experimental groups where bacterial DNA burden was increased in DIO (Figure 2).

View Article: PubMed Central - PubMed

ABSTRACT

Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high-fat diet-induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil- and macrophage-based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi-infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high-fat diet, toll-like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow-derived macrophages from obese, B. burgdorferi-infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice.

No MeSH data available.


Related in: MedlinePlus