Biology subjects

Campbell, R.

Publications and source records attributed to Campbell, R..

21 records · Page 2Linked to original sources

bioRxiv2020

Mucosal-associated invariant T (MAIT) cells mediate protective host responses in sepsis

Sepsis is a systemic inflammatory response to infection and a leading cause of death. Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in mucosal tissues that recognize bacterial ligands. We investigated MAIT cells during clinical and experimental sepsis, and their contribution to host responses. In experimental sepsis, MAIT-deficient mice had significantly increased mortality and bacterial load, and reduced tissue-specific cytokine responses. MAIT cells of WT mice expressed lower levels of IFN-{gamma} and IL-17a during sepsis compared to sham surgery, changes not seen in non-MAIT T cells. MAIT cells of patients presenting with sepsis were significantly reduced in frequency, more activated, and had decreased IFN-{gamma} production when stimulated, compared to healthy donors and paired 90-day post-sepsis samples. Our data suggest that MAIT cells are highly activated and become dysfunctional during clinical sepsis, and contribute to tissue-specific cytokine responses that are protective against mortality during experimental sepsis.

physiology↗

bioRxiv2019

Latent Toxoplasma gondii infection increases soluble mutant huntingtin and promotes neurodegeneration in the YAC128 mouse model of Huntington's disease

Toxoplasma gondii causes a prevalent neuroinvasive protozoal pathogen that in immune competent individuals results in latent infection characterized by intra-cellular parasite cysts in brain. Despite life-long infection, the role of latent toxoplasmosis on chronic neurodegenerative processes is poorly understood. Huntingtons disease (HD) is a progressive neurodegenerative disorder caused by a dominant CAG repeat expansion in the huntingtin gene (HTT) that results in the expression and accumulation of mutant huntingtin protein (mHTT). The mutant HD gene is fully penetrant. However, there is significant variability in disease progression that is in part explained by as yet unidentified environmental factors. The kynurenine pathway of tryptophan metabolism (KP) is an inflammatory pathway and its activation is implicated in HD pathogenesis. KP upregulation also occurs in response to infection with Toxoplasma gondii suggesting that the latent infection may promote HD. We discovered that mice on the FVB/NJ background develop latent toxoplasmosis following infection with the ME49 strain of T. gondii. This finding enabled us to address the hypothesis that latent toxoplasmosis potentiates disease in the YAC128 mouse model of HD, as these mice are maintained on the FVB/NJ background. Wild-type and HD mice were infected at 2-months of age. During the 10-month follow-up, infection had adverse effects on mice of both genotypes. However, YAC128 HD mice demonstrated specific vulnerability to latent toxoplasmosis, as demonstrated by the presence of increased striatal degeneration, high levels of the blood neurodegeneration marker neurofilament light protein, and elevated brain soluble mHTT. Our studies have uncovered a novel HD-infection interaction in mice that provides insights into the large variability of the human HD phenotype.

neuroscience↗

bioRxiv2017

Association between urinary biomarkers of total sugars and sucrose intake and BMI in a cross-sectional study

Obesity is an important modifiable risk factors for chronic diseases. While there is increasing focus on the role of dietary sugars, there remains a paucity of data establishing the association between sugar intake and obesity in the general public. The objective of this study was to investigate associations of estimated sugar intake with odds for obesity in a representative samples of English adults. We used data from 434 participants of the 2005 Health Survey of England. Biomarkers for total sugar intake were measured in 24h urine samples and used to estimate intake. Linear and logistic regression analyses were used to investigate associations between estimated intake and measures of obesity (BMI, waist circumference and waist-to-hip ratio) and obesity risk., respectively. Estimated sugars intake was significantly associated with BMI, waist circumference and waist-to-hip ratio, and these associations remained significant after adjustment for estimated protein intake. Estimated sugars intake was also associated with increased odds for obesity based on BMI (OR 1.02; 95% CI 1.00; 1.04 per 10 g), waist-circumference (OR 1.03; 95% CI 1.01; 1.05) and waist-to-hip ratio (OR 1.04; 95% CI 1.02; 1.06); all OR estimates remained significant after adjusting for estimated protein intake. Our results show a significant association between biomarker-estimated total sugars intake and both measures of obesity and obesity risk, confirming positive associations between total sugar intake, measures of obesity and obesity risk. This biomarker could be used to monitor the efficacy of public health interventions.

epidemiology↗