Table 1.
The distinctive immune responses in various infectious diseases upon leptin treatment were summarized.
| Infectious group | Infectious species | Effect of leptin on the Immune response | Model used (in-vitro & in-vivo) | References |
|---|---|---|---|---|
| Bacterial disease | Mycobacterium tuberculosis | Increase IFNγ & TNF-α levels and PMN cells & functions. Increase T helper CD4 T cells & CD8 T cells activity. Improve Ag- specific antibody response. Restored DTH response and Granuloma formation. Reduced IL-6 cytokine and bacterial load. |
Mice and human | (30, 95, 111) |
| Klebsiella pneumonia | Increase phagocytosis index and Leukotriene synthesis. Improve defective alveolar macrophage phagocytosis. Restored CD11b expression level. Decrease bacterial load and reduce mortality. |
Mice | (112, 113) | |
| Pneumococcal pneumonia | Restored defective alveolar macrophage phagocytosis activity. Increase PMN H2O2 production. Reduced TNF-α, MIP-2, PGE2 in the lung. Improves pulmonary bacterial clearance and survival. |
Mice | (31, 114) | |
| Clostridium difficile | Leptin receptor Q223R mutation leads to defective STAT3 signaling pathway and associated with an increased risk of colitis. Mutation of tyrosine 1,138 in the intracellular domain of LepRb decreased mucosal chemokine and cell recruitment. Increases inflammation, colonic chemokine expression, and cellular recruitment. Improve the bacterial clearance. |
Mice | (33) | |
| Sepsis | Improve the Neutrophil function. Increase the phosphorylation of p38 MAP kinase. Control sepsis-induced organ damage Supresses IL-6 and MCP-1 level. Control the bacteraemia. |
Mice and rat | (32, 110, 115) | |
| Listeria monocytogenes | Induce CD11b expression on neutrophils and lower the apoptosis. Induce effective bacterial phagocytosis and lymphocytic apoptosis in sever immune-deficiency. Improvement of anti-listerial resistance and the MCP-1 mRNA expression. Decrease defective MCP-1 expression in the liver. Control the bacteraemia. |
Mice | (116, 117) | |
| Helicobactor pylori | Increase mucosal leptin in the infected patients compare to uninfected patients. Amount of gastric leptin correlated positively with the mucosal levels of IL-1β and IL-6, but not IL-8 cytokine. Increase of gastric leptin expression during infection may have a local rather than systemic action. Increase in serum leptin concentration. Circulating leptin correlated with body mass index, but not with bacterial load. There was no change in plasma leptin levels following cure of the infection. |
Mice and human | (118–121) | |
| Viral disease | Influenza A/H1N1 pneumonia | Global deficiency of leptin receptor (db/db) have worsened survival following influenza A infection. Leptin receptor deficiency impaired viral clearance & diminished the IFN-γ levels. Loss of leptin receptor within lung epithelium or within macrophages is not associated with worsened lung injury or mortality following infection. Decrease proinflammatory cytokines IL-6 and IL-1β level and increase survival. Disruption of leptin signaling in T cells limits worsened the pH1N1 dependent mortality and infection severity. |
Human and mice | (34, 122–125) |
| Respiratory Syncytial Virus | Promoted Th17 subset differentiation. Suppressed Th2 subset differentiation. Increased phosphorylation of ERK1/2 in peripheral Lymphocytes. |
Human | (126) | |
| HIV | Leptin inhibits ROS and control oxidative burst mechanism in HIV+ monocyte patients. Leptin receptor (ob-R) expression increased in HIV+ PBMCs than control. Serum leptin level positively correlated with CD4+ T lymphocyte during antiviral therapy in HIV patients. Supresses SOCS3 & mTOR expression and Th2 subset differentiation. Reduced viral load. |
Human and mice (in-vitro & in-vivo) | (35, 127–129) | |
| Parasitic disease | Leishmania major/Leishmania donovani | Activates macrophage phagocytosis and ROS induction. Enhances the phosphorylation of Erk1/2 & Akt in macrophages. Increases IFN-γ, IL12, IL-1β secretion in macrophage. Improve IFN-γ/IL-10 ratio, GrzA and Th1 cytokine response. Activate CD8+ T-cell compartment and reduces PD-1 & CTLA-4 expression. Increase IgG2a levels and improve IgG2a/IgG1 ratio. Improve granuloma formation and repaired tissue degeneration. Reduced parasite load in visceral organs. |
Human (THP-1 and PBMCs) Mice (in-vitro & in-vivo) |
(36, 49, 130–132) |
| Trypanosoma cruzi | Defective leptin receptors or reduction in leptin level increase parasitemia and mortality rate. Reconstitution of central leptin signaling in brain reduces tissue parasitism and mortality rates. Improve plasma cytokines and chemokine's. |
Mice | (37, 133–136) | |
| Entamoeba histolytica | Mutation in leptin receptor (LEPR Q223R). Substitution of arginine (223R) in the cytokine receptor homology domain 1 of LEPR are more susceptible than those have glutamine (223Q) amino acid. Q223R polymorphism also decreased leptin-dependent STAT3 activation and defective STAT3 signaling and increase susceptibility to liver & intestinal abscess. Q223R leptin receptor mutation results in defective neutrophil infiltration to the site of infection. Mutation of tyrosine 985 or 1138 in leptin receptor results in defective SHP2/ERK and STAT3 signaling. Leptin-mediated resistance to amebiasis requires leptin receptor signaling through both the STAT3 and SHP2/ERK pathways. Leptin promotes regeneration & mucin secretion by epithelial cell and control apoptosis & integrity in intestinal epithelium lining. Low serum leptin increase liver and intestinal abscess. Intestinal parasites deregulate the secretion of leptin and adiponectin and play a role in enteric parasitosis by modulating body immunity, food intake and blood chemistry. |
Human and mice | (38, 137–142) | |
| Plasmodium berghei ANKA parasite | Higher serum leptin levels. Increase mTORC1 (Mechanistic target of rapamycin complex 1) activity in CD4+ and CD8+ T cells in a dose dependent manner. Leptin act as downstream target for mTORC1 activity in T cells during ECM. The leptin gene mutation in ob/ob is associated with observed CM resistance phenotype. CM resistance phenotype is due to involvement of Th1 cytokines TNF-α and INF-γ in the regulatory cascade controlling inflammatory responses after malarial infections. |
Mice | (39, 143, 144) |