IFN-gamma (Interferon Gamma)

Iron Restriction (Nutritional Immunity)#

IFN-γ is the master activator of iron-restriction defense against intracellular pathogens. Upregulates ferroportin (iron export from macrophages → starves intracellular pathogens of iron). Upregulates ferritin (iron sequestration into storage).

Downregulates transferrin receptor (reduces iron import into infected cells).

This is the primary host defense against Chlamydia trachomatis—IFN-γ-induced iron starvation forces Chlamydia into its non-replicating persistent form.^{[1]Chen 2021 — Alterations of vaginal microbiota in women with infertility and Chlamydia trachomatis infectionChen H, Wang L, Zhao L et al. · 2021Open reference 1 ↓} Karen's Brain Primitive 2: what appears as iron deficiency may be host-directed iron restriction.

Disease Relevance#

ASD: IFN-γ elevated (5.96 vs. 3.50 pg/ml, p=0.001).^{[2]Cao 2021 — Dysbiotic Gut Microbiota and Dysregulation of Cytokine Profile in Children and Teens With Autism Spectrum DisorderXia Cao, Kevin Liu, Jun Liu et al. · 2021Open reference 2 ↓} Schizophrenia: Elevated in FEP; drives IDO-mediated tryptophan shunting.^{[3]Immune System Abnormalities in Schizophrenia: An Integrative View and Translational PerspectivesErmakov EA, Melamud MM, Buneva VN et al. · 2022Open reference 3 ↓}

MS: Virus-induced IFN-γ drives gut Dysbiosis and neuroinflammation;^{[4]Gut Dysbiosis and Neuroimmune Responses to Brain Infection with Theiler's Murine Encephalomyelitis VirusF. J. Carrillo-Salinas, L. Mestre, M. Mecha et al. · 2017Open reference 4 ↓} S. thermophilus suppresses IFN-γ in MS models.^{[5]Streptococcus thermophilus ST285 Alters Pro-Inflammatory to Anti-Inflammatory Cytokine Secretion against Multiple Sclerosis Peptide in MiceDargahi N, Matsoukas J, Apostolopoulos V · 2020Open reference 5 ↓}