Figure 2.

The possible model of Leptin and Immune response in malnutrition coupled infectious diseases. In malnutrition, low adipocyte mass causes a reduction of serum leptin level resultant impairment of normal macrophages and lymphocytes activities. Infected macrophages induce the SOCS1 & 3 proteins expression subsequently upregulates ROS scavenging enzyme Thioredoxin which leads to activates SHP1/PTPase molecules. SHP1/PTP1 negatively regulates the JAK/STAT, and MAP-Kinase pathways thus inhibiting IFN–inducible macrophage functions (increased IL-10 and TGF-β level and decreased the IL-12 cytokines in infected macrophage). IL-10 suppresses the NO activity and improves the parasite survival. TGF-β activates SHP1/PTPase activity in lymphocytes through TGF-β receptor (TBR) which leads to lymphocytes apoptosis. In contrast, Leptin treatment inactivated SHP1/PTPase directed pathways and reversed the macrophage activities by up-regulating the pro-inflammatory cytokines (IFNγ, TNF-α, and IL-12) secretion and NO expression. IL-12 cytokine released from activated macrophage upon leptin treatment inhibits the SHP1/PTPase dependent T lymphocytes apoptosis by activation of JAK/STAT pathway. Moreover, Leptin directly inhibits the FasL-dependent T lymphocytes apoptosis by the inhibition of the caspase 8 activity. Caspase-8 then promotes mitochondrial outer membrane permeabilization (MOMP) by diminishing the inhibitory effect of various antiapoptotic and proapoptotic molecules. MOMP results in cytochrome-c release from the mitochondria, enabling activation of a supramolecular complex, the apoptosome that activates caspase-3 to undertake apoptotic cell death (Suppressors of cytokine signaling: SOCS1 & 3; Protein tyrosine phosphatases: SHP1/PTP1, Mitochondrial membrane potential drop: MMP drop, and P: phosphorylation) (192–206).