Antibiotics may reduce the ability of immune cells

Antibiotics normally act in concert with an organism's immune system to eliminate an infection. However, the drugs can have broad side effects, including eliminating "good" bacteria in the course of fighting off a pathogen. Researchers has shown that antibiotics can also reduce the ability of mouse immune cells to kill bacteria, and that changes to the biochemical environment directly elicited by treatment can protect the bacterial pathogen.

Different types of antibiotics can damage mitochondria in mice and in human epithelial cells, and that bacterial susceptibility to drugs can be affected by small molecules, called metabolites, released by cells as intermediates of their metabolic reactions. Antibiotic treatment might further alter the infection microenvironment in ways that impact bacteria and immune cells.

To investigate, the team treated mice infected by Escherichia coli bacteria with a commonly used antibiotic called ciprofloxacin, administered through the animals' drinking water at concentrations relative to what a human would receive, and quantified the biochemical changes. The researchers found that the antibiotic treatment elicited systemic changes in metabolites-not by influencing the microbiome, but by acting directly on the mouse tissues.

On further investigation, the team determined that metabolites released by mouse cells made E. coli more resistant to ciprofloxacin. Antibiotic exposure also impaired immune function by inhibiting respiratory activity in immune cells: Macrophages treated with ciprofloxacin were less able to engulf and kill E. coli bacteria.
The results highlight the potential of antibiotics to modulate the immune system, and reveal the importance of the metabolic microenvironment in resolving an infection.
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Immune cells can repair damaged nerves

Immune cells fight infections, in a new study, scientists have discovered how they also help the nervous system remove debris, clearing the way for nerve regeneration after injury. Some immune cells- neutrophils can clean up nerve debris. Neutrophils are one of the most common types of immune cells and known to engulf microorganisms, but they are not associated with peripheral nerve damage caused by diabetes or trauma.

Damaged nerve cells produce a stream of molecular lures that specifically attract neutrophils to injury sites in mice. Damaged mouse sciatic nerves produced hundreds of times the normal amount of two "chemoattractant" molecules, Cxcl1 and Cxcl2, which attach to the surfaces of neutrophils and draw the immune cells into injured tissue.

Once at the injury site, the neutrophils engulf cellular debris caused by the nerve damage, tidying up the area so the cells can repair themselves. Without the cellular clearance mechanism, nerves can't properly regenerate after injury. The experiments included sorting immune cells found at injury sites by molecules on their cellular surfaces, and many hours looking at mouse cells through the microscope.

Several different cells pick up the slack in the absence of macrophages, it was the neutrophil that emerged as a major contributor to debris removal. We also discovered that when we depleted neutrophils, nerve debris clearance was significantly halted in both normal mice and mice lacking a major population of macrophages.

Without neutrophils, nerve cells could not properly clear debris. This could leads to new therapeutics designed to repair nerve cells damaged by neurodegenerative disease. The clearance of debris after an injury is necessary for effective nerve regeneration. Immunostimulant molecules that target neutrophils at nerve injury location might enhance clean-up and promote nerve cell repair. Immunostimulant molecules are used to treat chronic infections and immunodeficiency.
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Immune cells hinder metabolism in adult

Older people do not burn the energy stored in fat cells as efficiently as younger people, this leads to the accumulation of harmful belly fat. The underlying cause for this unresponsiveness in fat cells was unknown.

Researchers discovered a new type of macrophage that resides on the nerves in belly fat. These nerve-associated macrophages become inflamed with age and do not allow the neurotransmitters, which are chemical messengers, to function properly.
The researchers also isolated the immune cells from fat tissue of young and old mice, and then sequenced the genome to understand the problem.

They discovered that the aged macrophages can break down the neurotransmitters called catecholamines, and thus do not allow fat cells to supply the fuel when needed. Lowering a specific receptor that controls inflammation, the NLRP3 inflammasome, in aged macrophages, the catecholamines could act to induce fat breakdown, similar to that of young mice.

Researchers blocked an enzyme that is increased in aged macrophages, restoring normal fat metabolism in older mice, monoamine oxidase and MAOA, is prevented by existing drugs in the treatment of depression. When immune cell interact with nerves and fat cells to reduce belly fat, this enhance metabolism, improve performance and belly fat loss in older people.
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Poliovirus therapy activates immune response against cancer

An investigational therapy using modified poliovirus to attack cancer tumors appears to unleash the body's own capacity to fight malignancies by activating an inflammation process that prevent cancer cells to evade the immune system.

Glioblastoma is a lethal form of brain cancer. The research team elucidated how the poliovirus works not only to attack cancer cells directly, but also activates longer-lasting immune response that appears to inhibit regrowth of the tumor.

Using human melanoma and breast cancer cell lines, and then validating the findings in mouse models, the researchers found that the modified poliovirus therapy starts by attaching to malignant cells, which have an abundance of CD155 protein.

The CD155 protein is a poliovirus receptor. The modified virus then begins to attack the tumor cells, directly killing many, but not all. This releases tumor antigens. The second phase of assault is more complicated, by killing the cancer cells, the modified poliovirus triggers an alarm within the immune system, alerting the body's defenses to attack.

This appears to occur when the modified poliovirus infects dendritic cells and macrophages. Dendritic cells then present tumor to T cells to launch an immune response. Once the immune system is activated against the poliovirus-infected tumor, the cancer cells can no longer hide and they remain vulnerable to ongoing immune attack.

Poliovirus killed tumor cells and infected the antigen-presenting cells, which allows them to function in such a way that they can raise a T-cell response that can recognize and infiltrate a tumor. Poliovirus stimulates an innate inflammatory response.
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Bone marrow protein may be used for stem cell transplant

Bone marrow contains hematopoetic stem cells, the precursors to every blood cell type. These cells become after bone marrow transplants, bone marrow injury and during systemic infection, creating new blood cells, including immune cells.

Del-1 is a protein that plays a role in gum disease, it regulate the production of blood cells. Targeting it could be an effective way to improve stem cell transplants for both donors and recipients. Modulate levels of Del-1 in patients with certain blood cancers can enhance immune cell production.

Because the hematopoetic stem cell niche is so important for the creation of bone marrow and blood cells and because Del-1 is a soluble protein and is easily manipulated, it could be a target in many potential applications.

The researchers' investigations revealed that Del-1 was expressed by at least three cell types in the bone marrow that support hematopoetic stem cells: endothelial cells, CAR cells and osteoblasts.

Using mice deficient in Del-1, they found that the protein promotes proliferation and differentiation of hematopoetic stem cells, sending more of these progenitor cells down a path toward becoming myeloid cells, such as macrophages and neutrophils, rather than lymphocytes, such as T cells and B cells.

In bone marrow transplant experiments, researchers discovered that the presence of Del-1 in recipient
bone marrow is required for the transplanted stem cells to engraft in the recipient and to facilitate the process of myelopoesis, the production of myeloid cells.

When the researchers mimicked a systemic infection in mice, animals deficient in Del-1 were slower to begin making myeloid cells again compared to those with normal Del-1 levels.

The scientists see potential applications in bone marrow and stem cell transplants, for both donors and recipients. In donors, blocking the interaction between Del-1 and hematopoetic stem cells could enhance the mobilization of those progenitors into the bloodstream. This could be helpful for increasing donor cell numbers for transplantation.

Transplant recipients, on the other hand, may need enhanced Del-1 interaction to ensure the transplanted cells engraft and begin making new blood cells more rapidly. People undergoing chemotherapy who develop febrile neutropenia, associated with low levels of white blood cells, might benefit from the role of Del-1 in supporting the production of immune-related blood cells such as neutrophils.
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Human brain is one of the HIV reservoirs

Scientists have created a model that can monitor the movement and development of an HIV infection in the brain. HIV virus can move to brain of infected macrophage 14 days after infection.

Antiretroviral drugs cannot get into the brain easily, brain is one of the reservoirs of HIV virus. Scientists have confirmed that HIV can survive in another less-explored type of white blood cell.

It can also persist exclusively in macrophages, large white blood cells found in the liver, lung, bone marrow and brain. This is the reason why Antiretroviral drugs can suppress the virus but not being able to kill it.

There were some evidence of brain damage from early HIV infection. The
virus can still affect the brain even if there is undetectable levels of HIV in the blood.

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How your brain keeps you warm

Recent study from Icahn school of medicine at Mount Sinai explained how the body regulates it's production of heat.

Researchers had hypothesized that macrophages is responsible for keeping the body warm, the recent study suggests sympathetic nervous system.

Christoph Buettner, a professor of medicine led the research team. They focused on catecholamines, hormones released by the sympathetic nervous system to activate brown fat tissue.

Brown adipose is a fat tissue that burns energy and produce heat and keep us warm.

Dr Buettner suggested that one of the ways of controlling effects of diabetes and obesity is to regulate the production of heat and metabolism by the brain and the nervous system.

New HIV reservoir discovered by scientists

Scientists have discovered a new cell in human body where HIV persists in spite of treatment.

Researchers have tried to clear HIV virus from the white blood cells that is part of immune system.

The virus persists in macrophages of infected person, this shows that T cells and some other cells in the body can serve as reservoir for HIV.

Macrophages are large white blood cell in tissue and bloodstream, the discovery shows that macrophages can be infected and they respond to antiretroviral therapy.

Scientists discovered that macrophages can survive in the body and continue to attack the HIV positive patients when their is therapy interruption.

Victor Garcia, a professor of medicine, microbiology and immunology and his team are trying to find out how HIV continues in tissue macrophages during HIV treatment and how it respond to treatment.