Table 1.
Animal models investigating the relationship between helminths and diet-induced metabolic disorders.
Figure 1.
A possible schematic role of inflammatory cells networks on T2D and CVD.
(A) The situation in animal models of T2D and CVD without the presence of helminths and in humans living in affluent areas not endemic for helminths. (B) The situation in animal models in the presence of helminths and in humans living in areas endemic for helminths. Although it is known that genes and lifestyle factors are involved in the development of insulin resistance and cardiovascular disease, it is becoming increasingly accepted that the immune system and inflammation play an important role as well. Obese people with metabolic syndrome have a higher degree of inflammation, characterized by increased TNF, a cytokine associated with insulin resistance. When the balance of T cell subsets is disturbed, increased frequencies of pro-inflammatory T cells such as T helper (Th) 1 and Th17 can drive classically activated macrophages (CAMs) which release TNF and, when in metabolic organs such as the adipose tissue, can interfere with insulin signaling. There is also evidence that, under inflammatory conditions, mast cells (MCs) contribute to the pathogenesis of metabolic disorders. High-affinity IgE, present on MCs, can lead to degranulation and initiate inflammation when cross-linked (A). However, the immune system is also endowed with cells such as Th2 and Treg that can exert anti-inflammatory activity and counterbalance the effects of TNF. The balance between pro- and anti-inflammatory activities in the immune system would determine insulin sensitivity. The situation seems to be different in rural areas of LMICs where helminth infections are highly prevalent. Helminths need nutrients from their host for their growth and reproduction, and this might use the energy of their host and therefore forestall obesity and insulin resistance. However, helminths can also lead to the expansion of alternatively activated Th2 and Treg. Th2 cytokines result in increased eosinophilia (EO) and, when in adipose tissue, can lead to the alternative activation of macrophages in this metabolically active organ; the AAMs in turn release anti-inflammatory cytokines such as IL-10. The signaling pathways are currently being dissected, but so far there is evidence that this cascade of events involves the activation of PPAR, STAT6, and/or Akt. Moreover, it has been noted that when the immune system is exposed to chronic helminth infections, EO and MCs no longer behave as pro-inflammatory immune cells, and IgE under these conditions appears to be of low affinity showing poor functional activity in terms of inducing MC degranulation. Thus, in the presence of helminth infections, the immune system is in an anti-inflammatory mode that is considered to be disadvantageous to the development of T2D and CVD (B). The solid lines represent associations based on data available, while dotted lines represent theoretical associations that are yet to be tested.