What Is: Macrophage

A realistic scientific visualization of a macrophage, a crucial immune cell, actively engulfing bacteria with its extended pseudopods.
The image provides a detailed look at the cell's internal structure during this defense process.

Scientific Frontline: Extended "At a Glance" Summary: Macrophage

The Core Concept: A macrophage is a highly versatile and essential metazoan immune cell primarily known for its ability to engulf particulate matter (phagocytosis), while also acting as a central orchestrator of tissue homeostasis, morphogenesis, metabolic regulation, and the bridge between innate and adaptive immunity.

Key Distinction/Mechanism: Unlike the historical dogma that all macrophages continuously derive from circulating blood monocytes, modern immunology distinguishes self-renewing tissue-resident macrophages (derived from embryonic progenitors) from short-lived, monocyte-derived macrophages recruited only during acute inflammation. Mechanistically, macrophages operate via an active, receptor-mediated "zipper" mechanism, utilizing specialized surface receptors to recognize targets, trigger actin-driven engulfment, and process the engulfed material within a hostile, highly acidic phagolysosome.

A mysterious outbreak of bone-eating tb resembled an ancestral form

Scientific Frontline: "At a Glance" Summary: Tuberculosis Mutation and Mobility

• Main Discovery: Researchers identified that a highly mobile strain of tuberculosis capable of infecting bone tissue possesses an active secretion factor called EsxM, which closely resembles an ancestral bacterial lineage rather than modern lung-restricted strains.
• Methodology: Scientists conducted genetic sequencing on the infectious strain and compared its genetic variants against 225 tuberculosis strains, focusing on secreted factors. They further validated their findings by analyzing 3,236 strains and manipulating the EsxM factor in laboratory macrophage cultures to directly observe cellular mobility.
• Key Data: While tuberculosis spreads beyond the lungs in only 2 percent of typical United States cases, this specific outbreak resulted in severe bone infections in four out of six initially identified individuals, representing a highly anomalous transmission rate.
• Significance: The study reveals that modern tuberculosis strains have evolutionarily silenced the EsxM secretion factor to remain isolated in the lungs for optimal airborne transmission, whereas the ancestral active version promotes aggressive bacterial migration throughout the host's body.
• Future Application: Uncovering the genetic drivers of bacterial mobility provides a foundational understanding that could inform future targeted therapeutics designed to prevent tuberculosis and similar pathogens from disseminating into vulnerable extrapulmonary regions.
• Branch of Science: Molecular Genetics, Microbiology, Epidemiology, and Evolutionary Biology.
• Additional Detail: The ancestral lineage 1 of tuberculosis, which retains the active migratory EsxM secretion factor, is still actively circulating and is predominantly found in South and Southeast Asia.

Macrophage immune cells need constant reminders to retain memories of prior infections

Image Credit: © 2026 Gorin et al.
Originally published in Journal of Experimental Medicine

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Macrophages do not possess inherent long-term memory but instead rely on constant stimulation from residual interferon-gamma molecules sequestered on their surface to maintain a primed state against repeat infections.
• Methodology: Researchers exposed human macrophages to interferon-gamma, identifying that the resulting "enhancer" DNA domains were not permanent but were actively maintained by lingering cytokine signals; blocking these signals reversed the memory state.
• Key Data: Temporary exposure generated thousands of new genetic enhancers that persisted for days, yet these memory markers were rapidly erased when the residual surface-bound interferon-gamma was pharmacologically inhibited.
• Significance: The study fundamentally shifts the understanding of innate immune memory from a stable cellular reprogramming event to a reversible, environment-dependent condition driven by tissue "staining" with cytokines.
• Future Application: New treatments could target and erase maladaptive macrophage memories to resolve autoimmune disorders such as lupus, rheumatoid arthritis, and type 1 diabetes without permanently compromising the immune system.
• Branch of Science: Immunology and Molecular Genetics
• Additional Detail: Lead author Dr. Aleksandr Gorin describes the phenomenon as tissues being "stained" by cytokines, which creates a sustained signaling loop that keeps local macrophages on high alert.

Rebalancing the Gut: How AI Solved a 25-Year Crohn’s Disease Mystery

Electron micrographs show how macrophages expressing girdin neutralize pathogens by fusing phagosomes (P) with the cell’s lysosomes (L) to form phagolysosomes (PL), compartments where pathogens and cellular debris are broken down (left). This process is crucial for maintaining cellular homeostasis. In the absence of girdin, this fusion fails, allowing pathogens to evade degradation and escape neutralization (right).
Image Credit: UC San Diego Health Sciences

The human gut contains two types of macrophages, or specialized white blood cells, that have very different but equally important roles in maintaining balance in the digestive system. Inflammatory macrophages fight microbial infections, while non-inflammatory macrophages repair damaged tissue. In Crohn’s disease — a form of inflammatory bowel disease (IBD) — an imbalance between these two types of macrophages can result in chronic gut inflammation, damaging the intestinal wall and causing pain and other symptoms. 

Researchers at University of California San Diego School of Medicine have developed a new approach that integrates artificial intelligence (AI) with advanced molecular biology techniques to decode what determines whether a macrophage will become inflammatory or non-inflammatory. 

The study also resolves a longstanding mystery surrounding the role of a gene called NOD2 in this decision-making process. NOD2 was discovered in 2001 and is the first gene linked to a heightened risk for Crohn’s disease.

Rejuvenated immune cells can improve clearance of toxic waste from brain

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers determined that specialized immune cells surrounding the brain, known as parenchymal border macrophages, control the fluid flow responsible for sweeping toxic waste from the brain, and that rejuvenating these cells in older subjects restores efficient waste clearance.
• Methodology: Scientists examined the cerebrospinal fluid flow in mice by depleting and impairing their border macrophages, which predictably caused neurological debris to accumulate. They subsequently treated aged mice with an immune-stimulating protein to successfully restore macrophage activity and normalize fluid dynamics.
• Key Data: Human brain fluid flow naturally begins to decline at approximately age 50, a physiological phenomenon mirrored in older mice, which exhibit a severe scarcity of the specific border macrophages necessary for efficient waste clearance.
• Significance: This discovery reveals a highly accessible therapeutic target for neurodegenerative conditions, shifting the scientific focus from attempting to revive dead or dying neurons to modifying the immune cells located on the brain's periphery.
• Future Application: Pharmacological treatments that target, boost, or replace parenchymal border macrophages could be utilized to slow, delay, or prevent the progression of Alzheimer’s disease, Parkinson’s, and multiple sclerosis.
• Branch of Science: Neuroscience and Neuroimmunology

Small molecules transport iron in mice, and human cells to treat some forms of anemia

University of Illinois chemistry professor Martin D. Burke and graduate student Stella Ekaputri were part of a team that found a small molecule, hinokitiol, ferries iron out of liver cells lacking the protein that normally does the job and restores hemoglobin and red blood cell production.   
Photo Credit: Michelle Hassel

A natural small molecule derived from a cypress tree can transport iron in live mice and human cells lacking the protein that normally does the job, easing a buildup of iron in the liver and restoring hemoglobin and red blood cell production, a new study found.

Stemming from a collaboration between researchers at the University of Illinois Urbana Champaign, the University of Michigan, Ann Arbor and the University of Modena in Italy, the study demonstrated that the small molecule hinokitiol potentially could function as a “molecular prosthetic” when the iron-transporting protein ferroportin is missing or defective, offering a potential treatment path for ferroportin disease and certain kinds of anemia.

“This is a really striking demonstration in a whole animal model that an imperfect mimic of a missing protein can reestablish physiology, acting as a prosthesis on a molecular scale,” said study co-leader Dr. Martin D. Burke, a professor of chemistry at Illinois and a member of the Carle Illinois College of Medicine, as well as a medical doctor. “The implications are really quite broad with respect to other diseases caused by loss of protein function.”

Ferroportin is a protein that forms a channel for transporting iron in and out of cells. Ferroportin deficiency can be due to a genetic mutation or caused by inflammation or infection. Patients without the protein have an excess buildup of iron in the liver, spleen and bone marrow, particularly in a type of cell called a macrophage. Macrophages in the liver chew up old red blood cells and transport the iron in them for recycling into new red blood cells. However, without ferroportin, the iron builds up inside the cells and can’t be recycled, Burke said.

Mice study suggests metabolic diseases may be driven by gut microbiome, loss of ovarian hormones

Mice that received fecal implants from donors that had their ovaries removed gained more fat mass and had greater expression of liver genes associated with inflammation, Type 2 diabetes, fatty liver disease and atherosclerosis. The findings may shed light on the greater incidence of metabolic dysfunction in postmenopausal women. The team members included, from left: molecular and integrative physiology professor Erik R. Nelson; Kelly Swanson, the director of the Division of Nutritional Sciences and the Kraft Heinz Endowed Professor in Human Nutrition; and animal sciences professor Brett R. Loman.
  Photo Credit: Fred Zwicky

The gut microbiome interacts with the loss of female sex hormones to exacerbate metabolic disease, including weight gain, fat in the liver and the expression of genes linked with inflammation, researchers found in a new rodent study.

The findings, published in the journal Gut Microbes, may shed light on why women are at significantly greater risk of metabolic diseases such as obesity and Type 2 diabetes after menopause, when ovarian production of female sex hormones diminishes.

“Collectively, the findings demonstrate that removal of the ovaries and female hormones led to increased permeability and inflammation of the gut and metabolic organs, and the high-fat diet exacerbated these conditions,” said Kelly S. Swanson, the director of the Division of Nutritional Sciences and the Kraft Heinz Endowed Professor in Human Nutrition at the University of Illinois Urbana-Champaign who is a corresponding author of the paper.  “The results indicated that the gut microbiome responds to changes in female hormones and worsens metabolic dysfunction.”

How Tumors Make Immune Cells ‘Go Bad’

Jlenia Guarnerio, PhD

Investigators from Cedars-Sinai Cancer have discovered that cancerous tumors called soft-tissue sarcomas produce a protein that switches immune cells from tumor-attacking to tumor-promoting. The study, published today in the peer-reviewed journal Cell Reports, could lead to improved treatments for soft-tissue sarcomas.

The researchers focused on the tumor microenvironment—an ecosystem of blood vessels and other cells recruited by tumors to supply them with nutrients and help them survive.

“Tumors also recruit immune cells,” said Jlenia Guarnerio, PhD, a research scientist with Cedars-Sinai Cancer, assistant professor of Radiation Oncology and Biomedical Sciences and senior author of the study. “These immune cells should be able to recognize and attack the tumor cells, but we found that the tumor cells secrete a protein that changes their biology, so instead of killing tumor cells they actually do the opposite.”

Soft-tissue sarcoma is a rare type of cancer that forms in the muscle, fat, blood vessels, nerves, tendons and joint lining. It most commonly occurs in the arms, legs and abdomen, and kills more than 5,000 people in the U.S. each year, according to the American Cancer Society.

In comparing samples of a variety of soft-tissue sarcomas in humans and laboratory mice, Guarnerio and her team noted that most of these tumors have an abundance of immune cells called myeloid cells in their microenvironment.

“It was striking that such a large percentage of the immune cells were myeloid cells, and we thought that since they obviously weren’t killing the tumor cells, they must be doing something to promote tumor growth,” said Stephen Shiao, MD, PhD, division director of the Division of Radiation Biology, co-leader of the Translational Oncology Program and a co-author of the study. “And indeed, our analysis of tumor samples showed that many of the myeloid cells had adopted a tumor-promoting function.”

New understanding of how mesenchymal stromal cells benefit patients in cell therapy

Apoptotic MSC (red) being engulfed by a macrophage (green).

The therapeutic benefit to patients receiving mesenchymal stromal cell (MSC) therapy is not because the injected cells remain viable, but because of cell death, researchers at the Monash Biomedicine Discovery Institute (BDI) have found.

In recent years, significant efforts have been made to develop stem cell-based therapies for difficult-to-treat diseases. MSC therapy is regenerative cell-based therapy for the treatment of these diseases and has shown great promise.

The findings of the BDI study show the therapeutic effects of MSCs are due to the recipient’s immune cells responding to the MSCs undergoing a specific type of cell death, called apoptosis, after injection that brings about anti-inflammatory effects.

Apoptosis is not simply cell death. It is a regulated process that ensures dying cells do not activate unwanted inflammation but instead promote an anti-inflammatory environment.

These apoptotic cells produce extracellular factors that have anti-inflammatory or therapeutic effects which may be possible to harness as alternatives to cell-based therapies.

Led by Associate Professor Tracy Heng, the study found that by disabling apoptosis in MSCs, the cells became ineffective in mitigating disease in models of lung inflammation and multiple sclerosis, diseases in which MSCs are currently being trialed as therapeutic agents.

The findings have now been published in Nature Communications.

Study Identifies Key T Cells for Immunity Against Fungal Pneumonia

 GM-CSF+ and IL-17A+ lineages of T cells are instrumental in controlling many fungal and bacterial infections and implicated in autoimmune pathology. This study shows that GM-CSF expressing Tc17 cells are necessary for mediating fungal vaccine immunity without augmenting pathology.
Credit: Som Nanjappa

Researchers at the University of Illinois College of Veterinary Medicine have demonstrated in a mouse model that a specific type of T cell, one of the body’s potent immune defenses, produces cytokines that are necessary for the body to acquire immunity against fungal pathogens. This finding could be instrumental in developing novel, effective fungal vaccines.

Despite vaccines being hailed as one of the greatest achievements of medicine, responsible for controlling or eradicating numerous life-threatening infectious diseases, no vaccines have been licensed to prevent or control human fungal infections.

This lack proved especially deadly during the COVID-19 pandemic. In countries where steroids were widely used to suppress inflammation of the lungs, COVID-19 patients with preexisting conditions such as uncontrolled diabetes showed a greater likelihood of developing lethal fungal infections.

Putting the STING into cancer immunotherapy

Belcher and Hammond Lab researchers developed a cancer vaccine that could make checkpoint blockade therapies more effective for more patients.
Illustration Credit: Bendta Schroeder

Immune checkpoint blockade therapies have been revolutionary in the treatment of some cancer types, emerging as one of the most promising treatments for diseases such as melanoma, colon cancer, and non-small cell lung cancer.  

While in some cases checkpoint blockade therapies elicit a strong immune response that clears tumors, checkpoint inhibitors do not work for all tumor types or all patients. Moreover, some patients who do experience an initial benefit from these therapies see their cancers recur. Only a small minority of patients treated with checkpoint blockade therapies see lasting benefits. Researchers have developed various combination therapy strategies to overcome resistance to checkpoint blockade therapies, with the STING pathway emerging as one of the most attractive lines of inquiry.  

In a study appearing in Advanced Healthcare Materials, a team of MIT researchers engineered a therapeutic cancer vaccine capable of restoring STING signaling and eliminating the majority of tumors in mouse models of colon cancer and melanoma, with minimal side effects. The vaccine also inhibited metastasis in a breast cancer mouse model and prevented the recurrence of tumors in cured mice. 

Cholera bacteria form aggressive biofilm to kill immune cells

The cholera-pathogen Vibrio cholerae (blue) forms an aggressive biofilm on the surface of immune cells (red).
Video Credit: University of Basel, Biozentrum

Bacteria harness the power of communities. A research group at the University of Basel has now discovered that the bacterial pathogen that causes cholera forms a novel type of bacterial community on immune cells: an aggressive biofilm that is lethal for the cells. The study, recently published in the journal Cell, provides new insights into the infection strategies of pathogens.

Many bacteria adopt a fascinating defense strategy by forming communities on surfaces, known as biofilms. We encounter such biofilms in our daily lives, for example, as dental plaque in the mouth, slimy films on stones in water or even as part of our intestinal flora. Bacterial biofilms are intrinsically tolerant to antibiotics and can pose a significant threat in clinical settings when they colonize implants, catheters, or surgical instruments. This colonization enables pathogens to infiltrate our body and trigger infections that are difficult to combat by the immune system and with antibiotics.

Previously, it was assumed that bacteria form biofilms to defend and protect themselves. The research team led by Professor Knut Drescher at the Biozentrum, University of Basel, has now demonstrated, in their recently published “Cell” study, that bacteria form biofilms on the surface of immune cells. This previously unknown type of community differs from already known bacterial biofilms not only in its structure, but also in its function: instead of serving a protective purpose, this biofilm is an aggressive trait.

Immune system meets cancer: Checkpoint identified to fight solid tumor

Immunofluorescence image of the expression of PHGDH (red) and CD3 T cells (green) in cryosectioned AE17 mesothelioma.
Image Credit: Zhengnan Cai

Checkpoint PHDGH in tumor-associated macrophages influences immune response and tumor growth

A study by a scientific team from the University of Vienna and the MedUni Vienna, recently published in the top-class journal Cellular & Molecular Immunology, has a promising result from tumor research: The enzyme phosphoglycerate dehydrogenase (PHDGH) acts as a metabolic checkpoint in the function of tumor-associated macrophages (TAMs) and thus on tumor growth. Targeting PHGDH to modulate the cancer-fighting immune system could be a new starting point in cancer treatment and improve the effectiveness of clinical immunotherapies.

Our immune system constantly fights emerging cancer cells that arise from mutations. This process is controlled, among other things, by different types of macrophages. Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the tumor microenvironment. They come from tissue-resident immune cells circulating in the blood that penetrate the tumor and differentiate there in response to various messenger substances (cytokines) and growth factors. In most solid tumors, TAMs are paradoxically considered to be tumor-promoting ("protumorigenic") overall: they promote tumor growth and metastasis by suppressing the immune response, promoting the vascular supply to the tumor and also increasing resistance to drug therapies – i.e. they generally correlate with a poor prognosis for the affected patients. Previous attempts to influence TAMs proved unsatisfactory because many patients had only a limited response to these therapeutic approaches. This underlines the urgency of finding new active ingredients and strategies.

Boosting weak immune system: scientists find an unusual weapon against virus

An overview of how the method proposed by the Sieweke group boosts weak immune system. (A) M-CSF cytokine works in the bone marrow to promote generation of monocytes and macrophages, without disturbing the formation of other immune cells; (B) Monocytes and macrophages activate natural killer cells to enable them to target virus-infected cells and kill them through cell–cell contact and the release of toxic agents.
Illustration Credit: © EMBO
(CC BY 4.0 DEED)

Infections with cytomegalovirus (CMV) are extremely common and often pose no major threat to the vast majority of people. They can, however, be deadly for people whose immune system is weakened, e.g., after bone marrow transplantation. Current treatments against CMV infections are very limited and can have severe side effects. Researchers led by Prof. Michael Sieweke at the Center for Regenerative Therapies Dresden (CRTD) at TUD Dresden University of Technology and the Center of Immunology of Marseille Luminy (CIML) propose a new way to protect against CMV. Instead of targeting the virus, their approach boosts the weak immune system and lets it fight the virus on its own. The results were published in the journal EMBO Molecular Medicine.

Some viruses can be dormant throughout a person’s life and cause no harm but become dangerous when the immune system is weakened. One such virus is human cytomegalovirus (CMV). Harmless to the general public but life-threatening to patients with a suppressed immune system.

Plastic particles increase inflammation and cross barriers

Lukas Kenner, visiting professor, Department of Molecular Biology.
Photo Credit: Medizinische Universität Wien

Scientific Frontline: "At a Glance" Summary

• Core Discovery: Micro- and nanoplastics (MNPs) exacerbate chronic inflammatory bowel diseases (IBD) and penetrate biological barriers to accumulate in vital organs beyond the gastrointestinal tract.
• Methodology: Researchers utilized a mouse model of ulcerative colitis, orally administering polystyrene particles—a common plastic found in food packaging—to analyze molecular and histological interactions with the intestinal mucosa and immune system.
• Mechanism of Action: MNP exposure triggers pro-inflammatory activation of macrophages and induces gut dysbiosis, characterized by a decrease in beneficial bacterial species and an increase in potentially harmful, pro-inflammatory microbes.
• Data Point: Nanoplastic particles smaller than 0.0003 millimeters (0.3 micrometers) demonstrated the highest mobility, successfully traversing the intestinal barrier to deposit in the liver, kidneys, and bloodstream.
• Contextual Findings: The uptake of MNPs into the intestinal mucosa is significantly intensified during active inflammatory states, suggesting a feedback loop where existing inflammation facilitates further plastic accumulation.
• Primary Implication: MNPs are an underestimated environmental factor in the pathogenesis of chronic inflammatory diseases, highlighting an urgent need to evaluate the systemic health risks posed by the migration of the smallest particles into major organ systems.

Canine Ocular Melanosis

Pathophysiology, genomic architecture, clinical progression, and therapeutic management of canine ocular melanosis
Image Credit: Scientific Frontline

In the discipline of veterinary ophthalmology, few conditions present as complex a challenge as Canine Ocular Melanosis (OM). Predominantly affecting the Cairn Terrier, yet not exclusive to this breed. This hereditary disorder is characterized by a relentless, progressive infiltration of pigmented cells within the ocular tissues, leading to severe morbidity through the development of intractable secondary glaucoma. Historically and colloquially referred to as "pigmentary glaucoma," this terminology has largely been abandoned in the academic literature in favor of "ocular melanosis" to more accurately reflect the underlying pathological process: a primary proliferation and migration of melanocytes, rather than a passive dispersion of pigment granules as seen in human pigmentary glaucoma. The disease represents a significant welfare concern due to the chronic pain associated with ocular hypertension and the eventual, often bilateral, loss of vision. Furthermore, its entrenched status within the Cairn Terrier gene pool, driven by an autosomal dominant mode of inheritance and a late age of onset, poses a profound dilemma for breeders and geneticists alike.  

HIV can persist for years in myeloid cells of people on antiretroviral therapy

HIV, the AIDS virus (yellow), infecting a human cell
Image Credit: National Cancer Institute

Scientific Frontline: "At a Glance" Summary: HIV Persistence in Myeloid Cells

• Main Discovery: HIV can persist for years in myeloid cells, specifically short-lived monocytes and longer-lived monocyte-derived macrophages, in individuals who have been virally suppressed on antiretroviral therapy.
• Methodology: Researchers isolated monocytes from the blood of virally suppressed participants and cultured them with antiretroviral drugs. After the monocytes differentiated into macrophages, an immune activating agent and fresh white blood cells were introduced to track viral reactivation and spread over a 12-day period using a novel quantitative method.
• Key Data: Detectable levels of HIV genetic material were found in the myeloid cells of 30 participants who had been on antiretroviral therapy for at least five years. Furthermore, cell cultures from 5 out of 10 participants demonstrated that the virus in these macrophages could reactivate, produce more virus, and infect new cells.
• Significance: The identification of myeloid cells as a long-lived and stable reservoir capable of viral rebound challenges the prevailing scientific consensus that monocytes are too short-lived to significantly impede HIV eradication efforts.
• Future Application: HIV cure strategies must be fundamentally broadened beyond their current scope to simultaneously target and eradicate viral reservoirs in both CD4 T cells and myeloid cells.
• Branch of Science: Virology and Microbiology
• Additional Detail: The study was led by researchers at the Johns Hopkins University School of Medicine, funded by the National Institutes of Health, and published in the journal Nature Microbiology.