Impaired CD4+ and T-helper 17 cell memory response to Streptococcus pneumoniae is associated with elevated glucose and percent glycated hemoglobin A1c in Mexican Americans with type 2 diabetes mellitus

Abstract

Individuals with type 2 diabetes are significantly more susceptible to pneumococcal infections than healthy individuals of the same age. Increased susceptibility is the result of impairments in both innate and adaptive immune systems. Given the central role of T-helper 17 (Th17) and T-regulatory (Treg) cells in pneumococcal infection and their altered phenotype in diabetes, this study was designed to analyze the Th17 and Treg cell responses to a whole heat-killed capsular type 2 strain of Streptococcus pneumoniae. Patients with diabetes demonstrated a lower frequency of total CD+T-cells, which showed a significant inverse association with elevated fasting blood glucose. Measurement of specific subsets indicated that those with diabetes had, low intracellular levels of interleukin (IL)-17, and lower pathogen-specific memory CD4+ and IL-17+ cell numbers. No significant difference was observed in the frequency of CD4+ and Th17 cells between those with and without diabetes. However, stratification of data by obesity indicated a significant increase in frequency of CD4+ and Th17 cells in obese individuals with diabetes compared with nonobese individual with diabetes. The memory CD+T-cell response was associated inversely with both fasting blood glucose and percent glycated hemoglobin A1c. This study demonstrated that those with type 2 diabetes have a diminished pathogen-specific memory CD4+ and Th17 response, and low percentages of CD+T-cells in response to S. pneumoniae stimulation.

<p>The Effects of Type 2 Diabetes and Postoperative Pneumonia on the Mortality in Inpatients with Surgery</p>

“…28 In adaptive immunity, T2DM have a diminished pathogenspecific memory CD4+ and Th17 response, and low percentages of CD+T-cells in response to S. pneumoniae stimulation. 29 Second, hyperglycaemia also increased airway surface liquid glucose concentrations which drive the proliferation of bacteria. 30 Third, T2DM is associated with impaired pulmonary function and reduced cardiorespiratory fitness.…”

T-helper-1, T-helper-17, T-regulatory lymphocytes in hypertensive patients with diabetes mellitus type 2 or impaired glucose tolerance: association with clinical and metabolic parameters in a case control study

“…Exposure to chronic inflammation may diminish effector functions of T-lymphocytes, which may impair protection against infections and cause predisposition to cancer, which is typical to diabetic patients [32][33][34]. It had also been shown that patients with DM2 are characterized by lower numbers of Th17, specific to infectious pathogens [35].…”

Worldwide increase in diabetes: implications for tuberculosis control

“…Furthermore, CD4+ and T-helper 17 (Th-17) cell memory responses are impaired in diabetes and we have recently also found that neutrophils from diabetes patients producing neutrophil extracellular traps when exposed to Streptococcus pneumoniae exhibited impaired ability to kill bacteria. 62 Another emerging hypothesis is that the elevated levels in diabetes of cytokines IL-6 and IL-1β (which promote Th-17 cell differentiation) skews the balance of T-cells to produce higher levels of Th-17 cells and suppresses the levels of inflammation mediating regulatory T-cells. 63,64 Given the impairments that diabetes delivers to a whole range of poorly understood immune responses critical in TB, considerably more basic research is needed before we can have a sufficiently clear picture to design and develop targeted therapies.…”