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Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

Javid A, Zlotnikov N, Pětrošová H, Tang TT, Zhang Y, Bansal AK, Ebady R, Parikh M, Ahmed M, Sun C, Newbigging S, Kim YR, Santana Sosa M, Glogauer M, Moriarty TJ - PLoS ONE (2016)

Bottom Line: Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint.Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs.These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

View Article: PubMed Central - PubMed

Affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.

ABSTRACT
Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

No MeSH data available.


Related in: MedlinePlus

Neutropenia in B. burgdorferi-infected and mock-infected hyperglycemic mice.(A, B) Mean ±SEM numbers of circulating neutrophils in blood of C57BL/6 (A) and C3H/HeN mice (B). Neutrophils were enumerated by particle counting with a Coulter counter in blood drawn by cardiac puncture from B. burgdorferi-infected and mock-infected mice at 4 weeks post-infection (5–6 weeks of sustained hyperglycemia). N = 6–9 mice/group. Experimental groups: Normoglycemic mock-infected (Vh), hyperglycemic mock-infected (STZ), normoglycemic B. burgdorferi-infected (Vh+Bb), hyperglycemic B. burgdorferi-infected (STZ+Bb). Statistical analysis: Two-way ANOVA with Holm-Sidak post-tests. * indicates p<0.05 vs. Vehicle; # indicates p<0.05 vs. normoglycemic B. burgdorferi-infected (Vh+Bb) mice.
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pone.0158019.g004: Neutropenia in B. burgdorferi-infected and mock-infected hyperglycemic mice.(A, B) Mean ±SEM numbers of circulating neutrophils in blood of C57BL/6 (A) and C3H/HeN mice (B). Neutrophils were enumerated by particle counting with a Coulter counter in blood drawn by cardiac puncture from B. burgdorferi-infected and mock-infected mice at 4 weeks post-infection (5–6 weeks of sustained hyperglycemia). N = 6–9 mice/group. Experimental groups: Normoglycemic mock-infected (Vh), hyperglycemic mock-infected (STZ), normoglycemic B. burgdorferi-infected (Vh+Bb), hyperglycemic B. burgdorferi-infected (STZ+Bb). Statistical analysis: Two-way ANOVA with Holm-Sidak post-tests. * indicates p<0.05 vs. Vehicle; # indicates p<0.05 vs. normoglycemic B. burgdorferi-infected (Vh+Bb) mice.

Mentions: We first determined numbers of peripheral neutrophils in blood of C3H/HeN and C57BL/6 mice at 4 weeks post-infection after 5–6 weeks of sustained hyperglycemia (Fig 4). Neutrophil counts in mice were significantly reduced in both hyperglycemic C57BL/6 and C3H/HeN mice independent of infection status (Fig 4A and 4B). Importantly, significant neutropenia was present in hyperglycemic mice infected with B. burgdorferi (Fig 4A and 4B), indicating that B. burgdorferi infection was not sufficient to overcome deficits in neutrophil production and/or mobilization in bone marrow of diabetic animals.


Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

Javid A, Zlotnikov N, Pětrošová H, Tang TT, Zhang Y, Bansal AK, Ebady R, Parikh M, Ahmed M, Sun C, Newbigging S, Kim YR, Santana Sosa M, Glogauer M, Moriarty TJ - PLoS ONE (2016)

Neutropenia in B. burgdorferi-infected and mock-infected hyperglycemic mice.(A, B) Mean ±SEM numbers of circulating neutrophils in blood of C57BL/6 (A) and C3H/HeN mice (B). Neutrophils were enumerated by particle counting with a Coulter counter in blood drawn by cardiac puncture from B. burgdorferi-infected and mock-infected mice at 4 weeks post-infection (5–6 weeks of sustained hyperglycemia). N = 6–9 mice/group. Experimental groups: Normoglycemic mock-infected (Vh), hyperglycemic mock-infected (STZ), normoglycemic B. burgdorferi-infected (Vh+Bb), hyperglycemic B. burgdorferi-infected (STZ+Bb). Statistical analysis: Two-way ANOVA with Holm-Sidak post-tests. * indicates p<0.05 vs. Vehicle; # indicates p<0.05 vs. normoglycemic B. burgdorferi-infected (Vh+Bb) mice.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4920391&req=5

pone.0158019.g004: Neutropenia in B. burgdorferi-infected and mock-infected hyperglycemic mice.(A, B) Mean ±SEM numbers of circulating neutrophils in blood of C57BL/6 (A) and C3H/HeN mice (B). Neutrophils were enumerated by particle counting with a Coulter counter in blood drawn by cardiac puncture from B. burgdorferi-infected and mock-infected mice at 4 weeks post-infection (5–6 weeks of sustained hyperglycemia). N = 6–9 mice/group. Experimental groups: Normoglycemic mock-infected (Vh), hyperglycemic mock-infected (STZ), normoglycemic B. burgdorferi-infected (Vh+Bb), hyperglycemic B. burgdorferi-infected (STZ+Bb). Statistical analysis: Two-way ANOVA with Holm-Sidak post-tests. * indicates p<0.05 vs. Vehicle; # indicates p<0.05 vs. normoglycemic B. burgdorferi-infected (Vh+Bb) mice.
Mentions: We first determined numbers of peripheral neutrophils in blood of C3H/HeN and C57BL/6 mice at 4 weeks post-infection after 5–6 weeks of sustained hyperglycemia (Fig 4). Neutrophil counts in mice were significantly reduced in both hyperglycemic C57BL/6 and C3H/HeN mice independent of infection status (Fig 4A and 4B). Importantly, significant neutropenia was present in hyperglycemic mice infected with B. burgdorferi (Fig 4A and 4B), indicating that B. burgdorferi infection was not sufficient to overcome deficits in neutrophil production and/or mobilization in bone marrow of diabetic animals.

Bottom Line: Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint.Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs.These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

View Article: PubMed Central - PubMed

Affiliation: Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Fitzgerald Building, Room 241, 150 College Street, Toronto, Ontario, M5S 3E2, Canada.

ABSTRACT
Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

No MeSH data available.


Related in: MedlinePlus