mSphere of Influence: the Key Role of Neutrophils in Tuberculosis and Type 2 Diabetes Comorbidity

ABSTRACT Annie Mayer Bridwell works in the field of tuberculosis pathogenesis from the host perspective. She is fascinated by comorbidities, and in this paper, she reflects on three publications that shaped her model of neutrophil-centric pathology in tuberculosis and type 2 diabetes comorbidity. She explains that “Systems immunology of diabetes-tuberculosis comorbidity reveals signatures of disease complications” (C. A. Prada-Medina, K. F. Fukutani, N. Pavan Kumar, L. Gil-Santana, et al., Sci Rep 7:1999, 2017, https://doi.org/10.1038/s41598-017-01767-4) led her to consider neutrophils as a central immunological player in comorbid patients. “Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis” (L. Moreira-Teixeira, P. J. Stimpson, E. Stavropoulos, S. Hadebe, et al., Nat Commun 11:5566, 2020, https://doi.org/10.1038/s41467-020-19412-6) and “Diabetes primes neutrophils to undergo NETosis, which impairs wound healing” (S. L. Wong, M. Demers, K. Martinod, M. Gallant, et al., Nat Med 21:815–819, 2015, https://doi.org/10.1038/nm.3887) then shed light on neutrophil extracellular trap (NET) formation as a common pathological feature of dysregulated neutrophils in tuberculosis and diabetes, respectively. Together, these works laid the foundation for Dr. Mayer Bridwell's interest in metabolic regulation of NETosis during TB infection and diabetes comorbidity.

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No Association Between Statin Use and the Prognosis of Endometrial Cancer in Women With Type 2 Diabetes

Frontiers in Pharmacology ◽

10.3389/fphar.2021.621180 ◽

2021 ◽

Vol 12 ◽

Author(s):

Elina Urpilainen ◽

Anne Ahtikoski ◽

Reetta Arima ◽

Ulla Puistola ◽

Peeter Karihtala

Keyword(s):

Type 2 Diabetes ◽

Endometrial Cancer ◽

Cancer Diagnosis ◽

Progression Free Survival ◽

Epidemiological Studies ◽

University Hospital ◽

Type I ◽

Statin Use

Preclinical studies have suggested statins have antiproliferative and anti-metastatic effects on endometrial cancer cells. Similarly, most previous epidemiological studies have reported a better prognosis of endometrial cancer in patients who used statins. In this study, we explored the role of statins in the prognosis of endometrial cancer in women with type 2 diabetes in a hospital-based cohort. This retrospective cohort consisted of 119 women with type 2 diabetes who were diagnosed and treated for endometrial cancer at Oulu University Hospital, Finland, between 2007 and 2014. The patients were classified as statin users (n = 58) and nonusers (n = 61) based on the type of medication they were using at the time of endometrial cancer diagnosis. Statin use showed no association with progression-free survival or overall survival in the whole cohort nor the subgroups with type I or type II histology, in lower or higher body mass index groups, or at an early or advanced stage. The results remained similar in the multivariate analysis after adjusting for the patient’s age, cancer stage, and histology. Furthermore, statin use seemed not to have any association with most of the prognostic factors at the time of endometrial cancer diagnosis.

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The role of gut microbiota in metabolic regulation

Diabetes Mellitus ◽

10.14341/dm7704 ◽

2016 ◽

Vol 19 (4) ◽

pp. 280-285 ◽

Cited By ~ 1

Author(s):

Ekaterina N. Kravchuk ◽

Alexander E. Neimark ◽

Elena N. Grineva ◽

Mikhail M. Galagudza

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Intestinal Microbiota ◽

Metabolic Regulation ◽

Modern Society ◽

Pathological Process ◽

Energy Regulation ◽

Huge Amount

Obesity and metabolic syndrome are among the major problems of modern society. The increase in obesity is associated with a corresponding increase in type 2 diabetes, cardiovascular disease and cancer. A huge amount of scientific research has been devoted to the development of methods to reduce obesity and its complications. In recent years, attention has shifted towards studying the intestinal microbiota not only as a possible component of the pathological process but also as a target of therapeutic intervention. Recent evidence, primarily from investigations in animal models, suggests that the intestinal microbiota affects nutrient acquisition and energy regulation. This review will discuss the role of the intestinal microbiota in metabolic processes as well as the latest developments on the improvement of disturbances specific to obesity and metabolic syndrome.

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FTO suppresses STAT3 activation and modulates proinflammatory interferon-stimulated gene expression

10.1101/2021.07.23.453596 ◽

2021 ◽

Author(s):

Michael J McFadden ◽

Matthew T. Sacco ◽

Kristen A. Murphy ◽

Moonhee Park ◽

Nandan S. Gokhale ◽

...

Keyword(s):

Gene Expression ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Type I Interferon ◽

Type I ◽

Type I Ifn ◽

Rna Modifications ◽

Inflammatory Genes

Signaling initiated by type I interferon (IFN) results in the induction of hundreds of IFN-stimulated genes (ISGs). The type I IFN response is important for antiviral restriction, but aberrant activation of this response can lead to inflammation and autoimmunity. Regulation of this response is incompletely understood. We previously reported that the mRNA modification m6A and its deposition enzymes, METTL3 and METTL14 (METTL3/14), promote the type I IFN response by directly modifying the mRNA of a subset of ISGs to enhance their translation. Here, we determined the role of the RNA demethylase FTO in the type I IFN response. FTO, which can remove either m6A or the cap-adjacent m6Am RNA modifications, has previously been associated with obesity and body mass index, type 2 diabetes, cardiovascular disease, and inflammation. We found that FTO suppresses the transcription of a distinct set of ISGs, including many known pro-inflammatory genes, and that this regulation is not through the actions of FTO on m6Am. Further, we found that depletion of FTO led to activation of STAT3, a transcription factor that mediates responses to various cytokines, but whose role in the type I IFN response is not well understood. This activation of STAT3 increased the expression of a subset of ISGs. Importantly, this increased ISG induction resulting from FTO depletion was partially ablated by depletion of STAT3. Together, these results reveal that FTO negatively regulates STAT3-mediated signaling that induces proinflammatory ISGs during the IFN response, highlighting an important role for FTO in suppression of inflammatory genes.

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