Hyperglycemic conditions inhibit C3-mediated immunologic control of Staphylococcus aureus

Hair, Pamela S.; Echague, Charlene G.; Rohn, Reuben D.; Krishna, Neel K.; Nyalwidhe, Julius O.; Cunnion, Kenji M.

doi:10.1186/1479-5876-10-35

Cited by 47 publications

(42 citation statements)

References 51 publications

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“…In diabetics there appears to be a lower percentage of CR3-positive monocytes, and in a separate study anti-PspA antibodies to S. pneumonia displayed reduced capacity for C3 deposition that was proportional to glucose control 16;17 Hyperglycemia has been associated with induction of structural changes on C3 that inhibit C3-mediated effector functions to S. aureus . 40 We are beginning to assess if there are defects in the complement components in serum and monocytes that explain the reduced association of M. tuberculosis , but we cannot exclude abnormalities in other heat-labile components of the immune system, such as cytokines.…”

Section: Discussionmentioning

confidence: 99%

Reduced Mycobacterium tuberculosis association with monocytes from diabetes patients that have poor glucose control

Gómez¹,

Twahirwa²,

Schlesinger³

et al. 2013

Tuberculosis

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The re-emerging importance of type 2 diabetes mellitus (DM) to tuberculosis (TB) control is of growing concern, but the basis for this relationship is poorly understood. Given the importance of mononuclear phagocytes for TB control and the reported alterations in monocytes of DM patients, we evaluated whether the initial interaction between both was affected in diabetics. M. tuberculosis-naïve individuals with and without DM were group matched by age and gender and the efficiency of M. tuberculosis association (attachment and ingestion) with their monocytes was assessed in the presence of autologous serum. The association of M. tuberculosis with monocytes was significantly lower in diabetics (19.2±6.1) than non-diabetics (27.5±7.9; p=0.02). Multivariate analysis controlling for host sociodemographics, DM characteristics and serum lipids indicated that male gender (p=0.04) and poorly-controlled DM (high HbA1c and hyperglycemia; p=0.01) were significantly associated with the lower interaction of M. tuberculosis with monocytes. Serum heat-inactivation reduced the association of M. tuberculosis to similar levels in both study groups (p=0.69) suggesting alterations in the complement pathway of DM patients. These findings suggest an altered route of entry of the pathogen in DM patients that may influence the downstream activation of signaling pathways in the monocyte and the survival of mycobacteria.

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Section: Discussionmentioning

confidence: 99%

Reduced Mycobacterium tuberculosis association with monocytes from diabetes patients that have poor glucose control

Gómez¹,

Twahirwa²,

Schlesinger³

et al. 2013

Tuberculosis

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“…Of the 23 experiments reporting data, obesity significantly increased blood or tissue bacteria or virus counts in 8 experiments and no experiment reported a decrease. Obesity-related insulin resistance and hyperglycemia or other changes may have impaired microbial clearance and worsened survival and organ injury [31][32][33][34][35][36][37][38][39]. Blood and tissue inflammatory cytokine levels including either TNF-α, IL-1b, IL-6, IL-10, or MIP-2a were also increased with obesity in 22 of 30 cases and may have contributed to inflammatory organ injury and worsened survival.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Obesity on Outcome in Preclinical Animal Models of Infection and Sepsis: A Systematic Review and Meta-Analysis

Pepper

Sun

et al. 2020

Journal of Obesity

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Background. Clinical studies suggest obesity paradoxically increases survival during bacterial infection and sepsis but decreases it with influenza, but these studies are observational. By contrast, animal studies of obesity in infection can prospectively compare obese versus nonobese controls. We performed a systematic review and meta-analysis of animal investigations to further examine obesity’s survival effect in infection and sepsis. Methods. Databases were searched for studies comparing survival in obese versus nonobese animals following bacteria, lipopolysaccharide, or influenza virus challenges. Results. Twenty-one studies (761 obese and 603 control animals) met the inclusion criteria. Obesity reduced survival in 19 studies (11 significantly) and the odds ratio (95% CI) of survival (0.21(0.13, 0.35); I2 = 64%, p<0.01p < 0.01) but with high heterogeneity. Obesity reduced survival (1) consistently in both single-strain bacteria- and lipopolysaccharide-challenged studies (n = 6 studies, 0.21(0.13, 0.34); I2 = 31%, p=0.20 and n = 5, 0.22(0.13, 0.36); I2 = 0%, p=0.59, respectively), (2) not significantly with cecal ligation and puncture (n = 4, 0.72(0.08, 6.23); I2 = 75%, p<0.01), and (3) significantly with influenza but with high heterogeneity (n = 6, 0.12(0.04, 0.34); I2 = 73%, p<0.01). Obesity’s survival effects did not differ significantly comparing the four challenge types (p=0.49). Animal models did not include antimicrobials or glycemic control and study quality was low. Conclusions. Preclinical and clinical studies together emphasize the need for prospective studies in patients accurately assessing obesity’s impact on survival during severe infection.

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“…Studies unrelated to TB show that transient or chronic hyperglycemia alters immune function. 30,31 The chronic up-regulation of glucose can lead to the abnormal accumulation of advanced glycation end products (AGE) that are highly reactive and can bind and modify immune response molecules (e.g. antibodies, complement).…”

Section: Mechanisms For Dysfunctional Immunity To Mtb In Dmmentioning

confidence: 99%

Host-pathogen interactions in tuberculosis patients with type 2 diabetes mellitus

Restrepo¹,

Schlesinger²

2013

Tuberculosis

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Tuberculosis (TB) is known to be fueled by HIV as well as social and economic factors. With progression of the diabetes mellitus (DM) pandemic in countries where TB is also endemic, focus is increasing on the potential links between DM and TB. Despite the magnitude of the DM-TB association woldwide, it is striking how little we know about the underlying biology that promotes this association which is a major concern to public health. In this review we summarize current findings regarding the alterations in the innate and adaptive immune responses of DM patients to Mycobacterium tuberculosis (Mtb). Current findings suggest underperforming innate immunity followed by a hyper-reactive cellular response to Mtb, but the contribution of these altered responses to TB susceptibility or to the more adverse clinical outcomes of TB patients with DM remains unclear. Elucidating the basic mechanisms underlying the higher susceptibility of DM patients to TB should lead to a strategy for stratification of the millions of DM patients worldwide into those with the highest TB risk for targeted TB prevention.

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Hyperglycemic conditions inhibit C3-mediated immunologic control of Staphylococcus aureus

Cited by 47 publications

References 51 publications

Reduced Mycobacterium tuberculosis association with monocytes from diabetes patients that have poor glucose control

Reduced Mycobacterium tuberculosis association with monocytes from diabetes patients that have poor glucose control

The Effects of Obesity on Outcome in Preclinical Animal Models of Infection and Sepsis: A Systematic Review and Meta-Analysis

Host-pathogen interactions in tuberculosis patients with type 2 diabetes mellitus

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