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Results for “GIMAPs”

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PubMed2024

Conservation of antiviral systems across domains of life reveals immune genes in humans.

Deciphering the immune organization of eukaryotes is important for human health and for understanding ecosystems. The recent discovery of antiphage systems revealed that various eukaryotic immune proteins originate from prokaryotic antiphage systems. However, whether bacterial antiphage proteins can illuminate immune organization in eukaryotes remains unexplored. Here, we use a phylogeny-driven approach to uncover eukaryotic immune proteins by searching for homologs of bacterial antiphage systems. We demonstrate that proteins displaying sequence similarity with recently discovered antiphage systems are widespread in eukaryotes and maintain a role in human immunity. Two eukaryotic proteins of the anti-transposon piRNA pathway are evolutionarily linked to the antiphage system Mokosh. Additionally, human GTPases of immunity-associated proteins (GIMAPs) as well as two genes encoded in microsynteny, FHAD1 and CTRC, are respectively related to the Eleos and Lamassu prokaryotic systems and exhibit antiviral activity. Our work illustrates how comparative genomics of immune mechanisms can uncover defense genes in eukaryotes.

Humans↗

PubMed2026

Comparative Transcriptomic Analysis of Human Macrophages During Mycobacterium avium Versus Mycobacterium tuberculosis Infection.

The treatment of Mycobacterium avium (Mav) infection, responsible for over 80% of nontuberculous mycobacterial pulmonary disease, remains challenging due to rising antibiotic resistance and unsatisfactory success rates. Hence, there is a need for a deeper understanding of host-pathogen interactions to inform the development of alternative therapeutic approaches, like host-directed therapy (HDT), aimed at improving host antimycobacterial defenses. However, compared to Mycobacterium tuberculosis (Mtb) infections, knowledge of host-pathogen interactions for Mav infection is still limited. To address this knowledge gap, we performed a genome-wide host transcriptomic analysis of Mav-infected primary human macrophages-the primary host cell-alongside Mtb-infected macrophages to leverage insights from Mtb research. Our findings show substantial overlap in the gene expression patterns between Mav-infected and Mtb-infected macrophages, including induction of cytokine responses and modulation of various G-protein coupled receptors (GPCRs) involved in (lipid-mediated) macrophage immune functions. Notable differences were observed in the expression of immediate early genes (IEGs), phospholipases, and genes of the GTPase of immunity-associated protein (GIMAP) family. This study laid a foundation for identifying both shared and Mav-specific host response pathways, providing direction for future investigations into host-pathogen interactions during Mav infection and the identification of novel targets for HDT.

Humans↗

PubMed2025

Quantitative temporal analysis of pancreatic islet T lymphocyte and macrophage infiltration heralded by serum IgE in congenic BioBreeding (BB) Gimap5-/- rats at risk for insulitis and acute onset diabetes.

OBJECTIVE AND DESIGN: The objective was to determine the association between serum IgE levels and the infiltration order of T lymphocytes and macrophages in pancreatic islets in relation to the loss of insulin and glucagon cells in presymptomatic congenic BB Gimap5-DP (Diabetes Prone) rats. MATERIAL: Congenic prediabetes BB Gimap5-DP and control Gimap5-DR (Diabetes Resistant) rats were followed every other day from 29 to 32 days of age until peak serum IgE (≤ 55 days of age). METHODS: Serum IgE was measured using ELISA. The HALO™ platform facilitated quantitative image analysis of infiltrating T lymphocytes, macrophages, and target organ insulin and glucagon cells. Whole genome sequencing (WGS) was employed to identify candidate type 1 diabetes genes. RESULTS: Serum IgE levels increased with age in normoglycemic BB Gimap5-DP rats. Quantification of infiltrating cells per mm2 in and around the islets indicated that T lymphocytes are the initial infiltrators, followed by macrophages. Elevated serum IgE levels inversely correlated with beta-cell mass (total mg insulin/mg pancreas). WGS refined the risk segment for islet inflammation to 1.02 Mbp, leaving 10 candidate genes, including Gimap4 and Gimap5. CONCLUSIONS: Elevated IgE levels herald T lymphocyte and macrophage infiltration. Pancreatic islet inflammation was linked to Gimap4, Gimap5, and other potential candidate genes on rat chromosome 4.

Animals↗