Endogenous intestinal microflora and environmental factors, such as diet, play a central role in immune homeostasis and reactivity. In addition, microflora and diet both influence body weight and insulin-resistance, notably through an action on adipose cells. Moreover, it is known since a long time that any disturbance in metabolism, like obesity, is associated with immune alteration, for example, inflammation. The purpose of this review is to provide an update on how nutrients-derived factors (mostly focusing on fatty acids and glucose) impact the innate and acquired immune systems, including the gut immune system and its associated bacterial flora. We will try to show the reader how the highly energy-demanding immune cells use glucose as a main source of fuel in a way similar to that of insulin-responsive adipose tissue and how Toll-like receptors (TLRs) of the innate immune system, which are found on immune cells, intestinal cells, and adipocytes, are presently viewed as essential actors in the complex balance ensuring bodily immune and metabolic health. Understanding more about these links will surely help to study and understand in a more fundamental way the common observation that eating healthy will keep you and your immune system healthy.

There is a finely tuned interplay between immune and neuroendocrine systems. Metabolic disturbances like obesity will have serious consequences on immunity both at the cellular and at the cytokine expression levels. Our in vivo results confirm the immune deficiency of ob/ob mice, leptin deficient and massively obese, characterized by a reduced Ag-specific T cell proliferation after keyhole limpet hemocyanin immunization. In this report, we show that dendritic cells (DCs), major APCs involved in T lymphocyte priming, are affected in obese mice. Both their function and their steady-state number are disturbed. We demonstrate that DCs from ob/ob mice are less potent in stimulation of allogenic T cells in vitro. This impaired functionality is not associated with altered expression of phenotypic markers but with the secretion of immunosuppressive cytokines such as TGF-β. Moreover, we show increased in vivo steady-state number of epidermal DCs in ob/ob mice, which is not due to a migratory defect. The ob/ob mice are characterized by the absence of functional leptin, a key adipokine linking nutrition, metabolism, and immune functions. Interestingly, intradermal injection of leptin is able to restore epidermal DC number in obese mice. Thus, DCs might be directly sensitive to metabolic disturbances, providing a partial explanation of the immunodeficiency associated with obesity.

Obesity is becoming one of the most serious public health problems in industrialized societies, due to the profound changes in lifestyle, and notably in nutrition. Beside diabetes, cardiovascular diseases or hypertension, increased susceptibility to infection is one of the pathological consequences of being overweight. In this paper, we have assessed the influence of a high‐fat diet (HFD) rich in saturated fatty acids on the immune system of DO11.10 mice, which are transgenic for a T‐cell receptor specifically recognizing a peptide of ovalbumin. We showed that the specific T‐cell immune response was impaired by high‐fat feeding, and that the expression of this defect is different depending on whether T cells are naive or Ag experienced. Indeed, on in vitro ovalbumin stimulation, spleen T cells from naive HFD‐fed transgenic mice showed proliferation similar to that of cells from standard diet (SD)‐fed mice, but exhibited a strong inflammatory profile as shown by the markedly increased IFN‐γ/IL‐4 ratio. Inversely, spleen T cells from ovalbumin‐immunized HFD mice were impaired in their Ag‐dependent proliferation compared to cells from SD mice. By co‐culture experiments, we showed that both T cells and antigen‐presenting cells were involved in this impairment. Moreover, in ovalbumin‐immunized HFD animals, a trend towards Th2 response was noted, compared to immunized SD mice. This data implies that naive T cells could participate actively in the low‐grade systemic inflammation observed in overweight patients. Moreover, the impaired activity of Ag‐experienced T cells could have major consequences both in defence against infection and/or in vaccination protocols.