How Gut Microbiota controls the Immune system

Gut-Centric Hypothesis: Prior Exposures to Microbes Explain Beneficial Roles of TREG

Stimulated by a gut-centric systemic homeostasis hypothesis, we set out to explore and explain the paradoxical roles of TREG in cancer using several different mouse models of cancer and adoptive cell transfer methodologies. It was found that TREG may suppress, promote, or have no effect in carcinogenesis depending upon their timing and prior exposure to gut bacterial antigens and presence of IL-10. Under some conditions, adoptive transfer of TREG rapidly led to apoptosis of emerging tumor cells. Using as a model organism an opportunistic pathogen,Helicobacter hepaticus, commonly residing in the lower bowel of mice, we have shown in Rag2-deficient mice (otherwise lacking lymphocytes) that gut microbiota modulate inflammatory bowel disease and inflammation-associated colon cancer, a cancer process inhibited by properly functioning IL-10-dependent TREG. Subsequently, by introducing H. hepaticus into the large bowel flora of mice lacking the APC tumor suppressor gene (ApcMin/+), we found that intestinal polypogenesis was greatly enhanced by bacteria and subsequently suppressed by immune-competent TREG. Furthermore, adenomas of infected ApcMin/+ mice progressed into adenocarcinoma, a transition atypical of polyps of aged-matched uninfected controls. Interestingly, ApcMin/+mice having H. hepaticus in their gut flora were prone to develop cancer in tissues distant from intestine, such as prostate and the mammary glands. H. hepaticus-induced tumorigenic events were inhibited by supplementation with TREG from immune-competent wild type donor mice.

A potent treatment to counteract these local and systemic H. hepaticus-induced tumorigenic events was supplementation with TREG in an IL-10-dependent manner. Purified TREG exhibited greatest anti-cancer potency when taken from donor mice previously colonized withH. hepaticus. By contrast, TREG taken from donor mice without prior H. hepaticus exposure were ineffective, and in some cases actually enhanced tumorigenesis. Based on these results, we theorize that the tumor microenvironment is subject to systemic inflammatory events arising from environmental exposures in the gastrointestinal tract (Figure 1). This microbe-inducible pro-inflammatory condition contributes to tumor trophic signaling. Interestingly, bacterial antigen triggered IL-10-dependent activities in the GI-tract impart sustained protection from the aforementioned events, resulting in immune cell recruitment, including TREG, which, by being more potent in their anti-inflammatory roles, work locally and systemically to suppress sepsis, myeloid precursor mobilization, and inflammatory signaling important in extra-intestinal cancer evolution. These systemic events comprise the tumor macroenvironment.

Front. Immunol., 07 April 2014 | doi: 10.3389/fimmu.2014.00157

Mental health and inflammation: new idea for fighting depression.

Science Translation

Mental illness affects nearly all people at some point or another in their life. This can be directly or indirectly through the suffering of a family member or close friend. Mental illness is the broad umbrella term we give to disorders that affect mental well-being. One of the most common forms of mental illness is depression with more than 10% of adults in the US reporting feeling depressed at some point in their life. Depression affects every aspect of your life including your relationships, your diet and health, and your work. At times in certain people it can become severe enough to require medical interventions and therapy. This is termed clinical or severe depression. Unfortunately, some people who suffer from severe depression will ultimately commit suicide as a way out of the pain. There is research to show that our current mode of treatment is inadequate at helping people with depression and…

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BioBit – Mitochondia, the little engines that power your cells

Apart from these functions, mitochondria also plays an important role in initiation of innate immune response through Grim 19 protein which interacts with Th19 cells in innate immune response

Science Translation

Mitochondria are little, bean shaped organelles inside you cells that are responsible for making the majority of the energy used by your cells.

Blausen_0644_Mitochondria Courtesy: staff

This often earns them the nickname “powerhouse of the cell”; however mitochondria perform many other important functions like:
  • Helping control cell growth
  • Helping cells and stem cells grow into the right type of cell (differentiation)
  • Helping cells to communicate with other parts of the cell or with other cells
  • Ensuring that when cells have to die, they do so in a clean, organized process called apoptosis

The amount of mitochondria within a cell can vary widely depending on that cells function. Typically, cells that need lots of energy, like liver cells, have lots of mitochondria while cells that need little energy, like red blood cells, have little or none.

Mitochondria have their own DNA that is separate from the DNA found in the nucleus…

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Breakthrough: Scientists in India make progress towards a viable Malaria vaccine

Interesting breakthrough


Anopheles mosquito. Pic credit:                                                      Anopheles mosquito
Pic credit:

Scientists from Jawaharlal Nehru University (JNU) and International Centre for Genetic engineering and biotechnology in New Delhi, India have discovered a novel molecule that could be a viable target for vaccines against malaria.

The quest for a malaria vaccine has been going on for decades now, with over 200 million people being affected annually, and  over 3.2 billion people at the risk of  malaria (WHO ). Most deaths occur among children living in Africa where a child dies every minute from malaria.  In the light of these concerns, the new findings by scientists in India give hope for a malaria vaccine in the near future.

Malaria is caused by a parasite called Plasmodium which spreads to people through the…

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Researchers at NTU discover the reason for Malaria’s drug resistance

Can targeting at the liver stage help in this regard


Pic courtesy: Nanyang technological university Pic courtesy: Nanyang technological university

Researchers at Singapore’s Nanyang Technological University, lead by Dr. Zbynek Bozdech have discovered the mechanism by which the malaria parasite is developing resistance to key front-line drugs used for its treatment, such as artemisinin.

Malaria is caused by a parasite, Plasmodium which is transmitted to humans via the bites of infected mosquitoes. They infect red blood cells causing symptoms such as fever and vomitting and if left untreated, could prove fatal. In 2013, an estimated 198 million cases of malaria were reported worldwide, with an estimated 584,000 deaths. One of the key intervention strategies to control malaria include artemisinin-based combination therapies and indoor residual spraying with insecticide to control the mosquitoes carrying the parasite.However, there is an emerging parasite resistance to artemisinin and if the mechanism by which the parasite is developing drug resistance is not understood, there could be a rise in global malaria…

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My Course sites

I have been teaching various courses in the M. Sc programme such as Reproductive Physiology, Biochemical Toxicology, Endocrinology and Vaccinology.

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