# Leishmania mediated regulation of host metabolism: impact on host immunity

**Authors:** Somtochukwu S. Onwah, Gaurav Gupta, Romaniya Zayats, Amol Singh Banga, Kashish Chhotaria, Gurtej Ahluwalia, Jude E. Uzonna

PMC · DOI: 10.3389/fimmu.2026.1750304 · Frontiers in Immunology · 2026-02-18

## TL;DR

This paper reviews how the Leishmania parasite manipulates host cell metabolism to avoid immune detection and suggests new ways to treat leishmaniasis.

## Contribution

The paper provides a comprehensive review of Leishmania's metabolic manipulation of host immune cells to evade immune responses.

## Key findings

- Leishmania exploits host metabolic pathways to survive in macrophages.
- The parasite modulates metabolism in immune cells like macrophages and T cells.
- Understanding these metabolic changes could lead to new vaccines and treatments.

## Abstract

Leishmaniasis, a vector-borne disease affecting millions worldwide, is caused by protozoan parasite Leishmania. In mammalian hosts, Leishmania survives in the hostile environment of macrophages by exploiting key metabolic pathways to evade their destruction and subvert the host immune responses. Understanding of how Leishmania alters host immune cell metabolism could reveal novel targets for vaccines and therapeutics for effective control of Leishmaniasis. This review focuses on Leishmania-induced modulation of host immune response, with particular focus on reprograming of key metabolic pathways in macrophages, dendritic cells, T cells and other immune cells.

## Linked entities

- **Diseases:** Leishmaniasis (MONDO:0011989)
- **Species:** Leishmania (taxon 5658)

## Full-text entities

- **Genes:** SLC7A5 (solute carrier family 7 member 5) [NCBI Gene 8140] {aka 4F2LC, CD98, D16S469E, E16, LAT1, MPE16}, Ldha (lactate dehydrogenase A) [NCBI Gene 16828] {aka Ldh1, Ldhm, l7R2}, Arg1 (arginase, liver) [NCBI Gene 11846] {aka AI, Arg-1, PGIF}, STAT6 (signal transducer and activator of transcription 6) [NCBI Gene 6778] {aka D12S1644, HIES6, IL-4-STAT, STAT6B, STAT6C}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Hif1a (hypoxia inducible factor 1, alpha subunit) [NCBI Gene 15251] {aka HIF-1-alpha, HIF1-alpha, HIF1alpha, MOP1, bHLHe78}, Slc2a1 (solute carrier family 2 (facilitated glucose transporter), member 1) [NCBI Gene 20525] {aka GT1, Glut-1, Glut1, M100200, Rgsc200}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Il13 (interleukin 13) [NCBI Gene 16163] {aka Il-13}, TBX21 (T-box transcription factor 21) [NCBI Gene 30009] {aka IMD88, T-PET, T-bet, TBET, TBLYM}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Phgdh (3-phosphoglycerate dehydrogenase) [NCBI Gene 236539] {aka 3-PGDH, 3PGDH, 4930479N23, A10, PGAD, PGD}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Pck1 (phosphoenolpyruvate carboxykinase 1, cytosolic) [NCBI Gene 18534] {aka PEPCK, PEPCK-C, Pck-1}, DLD (dihydrolipoamide dehydrogenase) [NCBI Gene 1738] {aka DLDD, DLDH, E3, GCSL, LAD, OGDC-E3}, Crtc2 (CREB regulated transcription coactivator 2) [NCBI Gene 74343] {aka 4632407F12Rik, Torc2}, Stat6 (signal transducer and activator of transcription 6) [NCBI Gene 20852], Cxcl14 (C-X-C motif chemokine ligand 14) [NCBI Gene 57266] {aka 1110031L23Rik, 1200006I23Rik, BMAC, BRAK, KS1, Kec}, S-adenosylmethionine decarboxylase [NCBI Gene 13385735], Trav6-3 (T cell receptor alpha variable 6-3) [NCBI Gene 328483] {aka Gm13948, Gm193, Gm4, TCR}, Pparg (peroxisome proliferator activated receptor gamma) [NCBI Gene 19016] {aka Nr1c3, PPAR-gamma, PPAR-gamma2, PPARgamma, PPARgamma2}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Il5 (interleukin 5) [NCBI Gene 16191] {aka Il-5}, PCK2 (phosphoenolpyruvate carboxykinase 2, mitochondrial) [NCBI Gene 5106] {aka PEPCK, PEPCK-M, PEPCK2, mtPCK2}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, Trypanothione reductase [NCBI Gene 13391295], Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Dld (dihydrolipoamide dehydrogenase) [NCBI Gene 13382], Pdcd1 (programmed cell death 1) [NCBI Gene 18566] {aka Ly101, PD-1, Pdc1}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, NOS2 (nitric oxide synthase 2) [NCBI Gene 4843] {aka HEP-NOS, INOS, NOS, NOS2A}, Rhoa (ras homolog family member A) [NCBI Gene 11848] {aka Arha, Arha1, Arha2}, Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 19013] {aka 4933429D07Rik, Nr1c1, PPAR-alpha, PPARalpha, Ppar}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, Cd28 (CD28 antigen) [NCBI Gene 12487], Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Myc (Myc proto-oncogene, bHLH transcription factor) [NCBI Gene 17869] {aka Myc2, Niard, Nird, bHLHe39}, Cd163 (CD163 antigen) [NCBI Gene 93671] {aka CD163v2, CD163v3}, IL13 (interleukin 13) [NCBI Gene 3596] {aka IL-13, P600}, PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468] {aka CIMT1, FPLD3, GLM1, NR1C3, PPARG1, PPARG2}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, ARG1 (arginase 1) [NCBI Gene 383], IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, FOXP3 (forkhead box P3) [NCBI Gene 50943] {aka AIID, DIETER, IPEX, JM2, PIDX, XPID}, IDO1 (indoleamine 2,3-dioxygenase 1) [NCBI Gene 3620] {aka IDO, IDO-1, INDO}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, CD46 (CD46 molecule) [NCBI Gene 4179] {aka AHUS2, MCP, MIC10, TLX, TRA2.10}
- **Diseases:** hepatosplenomegaly (MESH:C535727), L. amazonensis infection (MESH:D007239), Leishmania (MESH:D007896), DCL (MESH:D016774), L. infantum infection (MESH:D005767), cytotoxicity (MESH:D064420), asthma (MESH:D001249), Mucocutaneous leishmaniasis (MESH:D007897), Inflammation (MESH:D007249), metastasis (MESH:D009362), nutrient deficiency (MESH:D007153), skin lesions (MESH:D012871), PKDL (MESH:D007898), CL (MESH:D016773), hypoxia (MESH:D000860), sepsis (MESH:D018805), hypoxic (MESH:D002534), cutaneous lesion (MESH:D009059), parasitic infection (MESH:D010272), hypergammaglobulinemia (MESH:D006942)
- **Chemicals:** Amp-B (MESH:D000666), isocitrate (MESH:C034219), Thiol (MESH:D013438), LPG (MESH:C008290), lactate (MESH:D019344), aspartate (MESH:D001224), prostaglandin E. (MESH:D011458), heme (MESH:D006418), amino acid (MESH:D000596), miltefosine (MESH:C039128), Ergosterol (MESH:D004875), urea (MESH:D014508), NADPH (MESH:D009249), mannose-1-phosphate (MESH:C047217), G6P (MESH:D019298), decarboxylated S-adenosylmethionine (MESH:C012702), CoA (MESH:D003065), serine (MESH:D012694), triglyceride (MESH:D014280), azole (MESH:D001393), Putrescine (MESH:D011700), pentose phosphate (MESH:D010428), fatty acid (MESH:D005227), L-arginine (MESH:D001120), alanine (MESH:D000409), mannose-6-phosphate (MESH:C027693), SAG (MESH:D000967), TCA (MESH:D014233), rapamycin (MESH:D020123), creatine phosphate (MESH:D010725), carbon (MESH:D002244), creatine (MESH:D003401), succinate (MESH:D019802), glycerophosphocholine (MESH:D005997), pyruvate (MESH:D019289), hydroperoxides (MESH:D006861), metal (MESH:D008670), Ca2+ (-), itaconate (MESH:C005229), D, L-alpha-difluoro-methyl ornithine (MESH:D000518), L-ornithine (MESH:D009952), alpha-Ketoglutarate (MESH:D007656), sugar (MESH:D000073893), PUFA (MESH:D005231), Nomega-hydroxy-l-arginine (MESH:C068309), oxygen (MESH:D010100), Ambisome (MESH:C068538), NAD+ (MESH:D009243), glycolipid (MESH:D006017), glutaraldehyde (MESH:D005976), MDL73811 (MESH:C065859), glutamate (MESH:D018698), Spd (MESH:D013095), tryptophan (MESH:D014364), citrulline (MESH:D002956), zinc sulfate (MESH:D019287), alcohol (MESH:D000438), NO (MESH:D009569), cholesterol (MESH:D002784), Glucose (MESH:D005947)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Leishmania guyanensis (species) [taxon 5670], Canis lupus familiaris (dog, subspecies) [taxon 9615], Homo sapiens (human, species) [taxon 9606], Leishmania infantum (species) [taxon 5671], Leishmania (subgenus) [taxon 38568], Leishmania braziliensis (species) [taxon 5660], Leishmania donovani (species) [taxon 5661], Leishmania aethiopica (species) [taxon 5667], Leishmania mexicana (species) [taxon 5665]
- **Mutations:** G6P
- **Cell lines:** C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), Balb/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184)

## Full text

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## Figures

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## References

222 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956810/full.md

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Source: https://tomesphere.com/paper/PMC12956810