Toll-like receptors (TLRs) may need to cooperate with each other to be effective in detecting imminent infection and trigger immune responses. Understanding is still limited about the intracellular mechanism of this cooperation. We found that when certain TLRs are involved, dendritic cells (DCs) establish unidirectional intracellular cross-talk, in which the MyD88-independent TRIF-dependent pathway amplifies the MyD88-dependent DC function through a JNK-dependent mechanism. The amplified MyD88-dependent DC function determines the induction of the T cell response to a given vaccine in vivo. Therefore, our study revealed an underlying TLR mechanism governing the functional, nonrandom interplay among TLRs for recognition of combinatorial ligands that may be dangerous to the host, providing important guidance for design of novel synergistic molecular vaccine adjuvants.HIV ͉ innate immunity ͉ adjuvants ͉ MyD88 ͉ TRIF

Epidemiological studies have shown an inverse correlation between the incidence of lymphatic filariasis (LF) and the incidence of allergies and autoimmunity. However, the interrelationship between LF and type-2 diabetes is not known and hence, a cross sectional study to assess the baseline prevalence and the correlates of sero-positivity of LF among diabetic subjects was carried out (n = 1416) as part of the CURES study. There was a significant decrease in the prevalence of LF among diabetic subjects (both newly diagnosed [5.7%] and those under treatment [4.3%]) compared to pre-diabetic subjects [9.1%] (p = 0.0095) and non-diabetic subjects [10.4%] (p = 0.0463). A significant decrease in filarial antigen load (p = 0.04) was also seen among diabetic subjects. Serum cytokine levels of the pro-inflammatory cytokines—IL-6 and GM-CSF—were significantly lower in diabetic subjects who were LF positive, compared to those who were LF negative. There were, however, no significant differences in the levels of anti-inflammatory cytokines—IL-10, IL-13 and TGF-β—between the two groups. Although a direct causal link has yet to be shown, there appears to be a striking inverse relationship between the prevalence of LF and diabetes, which is reflected by a diminished pro-inflammatory cytokine response in Asian Indians with diabetes and concomitant LF.

BackgroundThe role played by T helper cytokines under chronic, low grade inflammation as seen in type-2 Diabetes Mellitus (T2DM) and Coronary Artery Disease (CAD) co-morbidity is less well studied. In the present study, we measured the serum levels of both Th1 and Th2 cytokines and correlated it with clinical risk factors for T2DM (Insulin Resistance (IR), Glycated haemoglobin (HbA1c)) and CAD (C-Reactive Protein (CRP), Intima Media Thickness (IMT) and Augmentation index (AGI)) in T2DM subjects with/without CAD.MethodologyThe study subjects were recruited from Chennai Urban Rural Epidemiology Study (CURES). Serum cytokine profile was determined by multiplex cytokine assay in Control (n = 61), T2DM (n = 60), CAD (n = 23) and T2DM-CAD (n = 21) subjects.ResultsT2DM subjects showed a mixed Th1-Th2 profile. CAD subjects presented a Th1 profile with modest Th2 suppression while T2DM-CAD subjects showed enhanced Th1 profile with strong suppression of Th2 cytokines. Both Th1 and Th2 cytokines showed a positive correlation with FPG, HbA1c, hsCRP, IMT and AGI. Logistic regression analysis revealed a significant association of IL-12 (OR = 9.3; 95% CI = 3.2-70.7; p = 0.016), IFN-γ (OR = 2.8; 95% CI = 2.7-2.9, p = 0.010), IL-4 (OR = 2.7; 95% CI 2.7-2.7, p = 0.010), IL-5 (OR = 1.1; 95% CI = 1.0-1.4; p = 0.003) and IL-13 (OR = 2; 95% CI = 1.7-2.6; p = 0.017) with T2DM-CAD.ConclusionIn conclusion, from the present study it appears that transition from T2DM or CAD to T2DM-CAD co-morbidity is associated with strong down regulation of Th2 cytokines and enhancement of Th1 responses.

Apart from pro-inflammatory cytokines, Th cytokines might play an important role in inflammation, IR, and MS.

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The role of inflammation in both diabetes and diabetic kidney disease (DKD) is becoming more widely accepted. However, the role of recently characterized T cell cytokines interleukin (IL)-9 and IL-17 in diabetes and especially DKD is less well studied. Transforming growth factor beta (TGF-β) controls the secretion of both of these cytokines. In this study, we estimated the levels of IL-9, IL-17, and TGF-β in the serum of subjects with normal glucose tolerance (NGT = 88) and subjects with type 2 diabetes without (diabetes mellitus (DM) = 65) and with DKD (DKD = 97) using enzyme-linked immunosorbent assay (ELISA), and we correlated these levels with the clinical risk factors of diabetes and DKD. IL-17 levels showed a serial decline and TGF-β levels showed a serial increase from NGT to DM to DKD (p < 0.001). However, the IL-9 levels were significantly reduced in the DM group compared to the NGT and DKD group (p < 0.001). While TGF-β and IL-17 showed a positive and negative correlation, respectively, with fasting and postprandial glucose levels and glycated hemoglobin (HbA1c), IL-9 showed positive correlation with urea and microalbuminuria. Apart from pro-inflammatory cytokines, T helper (Th) cytokines might play an important role in insulin resistance and DKD.

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