Olfaction-immune cells metabolic cross talk and its relevance in immune responses

Miss Sukanya Madhwal’s interview with Bio Patrika hosting “Vigyan Patrika”, a series of author interviews. Sukanya completed her Masters’s degree in Biotechnology from Banasthali Vidyapith, Rajasthan. After this, she served as a graduate teacher for one year at P.G. College, Kotdwara, Uttarakhand. In 2014, she qualified the JGEEBILS exam conducted by NCBS/TIFR and joined as a Research Scholar (Ph.D. student) in Dr. Tina Mukherjee’s lab at inStem. Her research has significantly contributed to uncovering key findings in Drosophila immunity. She further aspire to continue her research venture in the field of immunology. Besides work, she love reading non-fiction books, enjoy gardening and cooking delicious food. Here, Sukanya talks about her work titled “Metabolic control of cellular immune-competency by odors in Drosophila”, published as the first author in eLife, 2020.

How would you explain your paper’s key results to the non-scientific community?

 Olfaction, the sense of smelling the environment stimulates varied animal behavioral responses in search of food, mates, and avoiding danger. Beyond this, a compelling connection between olfaction and the immune system also exists. However, detailed understanding of the relevance of olfaction-immune connection in development and infection still lack in the field. Thus, we ventured into investigating olfaction and immune cells cross-talk and explored its relevance in immune responses utilizing Drosophila as a model system.

Employing various genetics tricks in Drosophila, we manipulated different components of the olfactory system and analyzed immune cell responses in development and immune-challenged conditions. Interestingly, we observed that animals with genetically perturbed smelling capabilities or those reared in conditions devoid of odors, when challenged with wasp infection, failed to sustain a potent repertoire of blood progenitor cells. And ultimately, they failed to generate a specialized immune cell type called lamellocytes which are necessary immune cell type required to combat the parasitic wasp infection. This finding showed a developmental role of odor sensing in establishing a competent pool of blood progenitor cells, important for overcoming parasitic wasp challenge. Mechanistically, we identified that odors stimulate, brain neuronal cells to release a metabolite called GABA (gamma-aminobutyric acid) into the hemolymph. GABA then reaches the lymph gland, a specialized hematopoietic organ that harbors an undifferentiated pool of blood progenitor cells and gives rise to mature blood cells. Within blood progenitor cells GABA is then transported inside and catabolized through a metabolic pathway called the GABA-shunt pathway. This metabolic cue and the functioning of GABA metabolic pathway within blood progenitor cells shape their competency for lamellocytes formation.

Interestingly, when animals during development were exposed to the predatory wasp’s odors showed superior wasps immune responses. Here, wasp’s odor perception elevated the metabolic cue between olfaction-immune cell cross-talk to boost their immune potential and generated more lamellocytes which thereby facilitated efficient immune response. Overall, this work highlights the importance of odors sensing by the animal in priming cellular-immunity.

What are the possible consequences of these findings for your research area?

This study extends our knowledge on the significance of the animal olfactory system and its influence on the immune cells. It shows during animal development; environmental odor modulates myeloid-progenitor metabolism and establishes blood-progenitor competency and immune-priming. Given many similarities between Drosophila and the mammalian system, it opens the door to test the existence of such sensory routes relevant during the development of human hematopoietic stem cells and progenitor cells. This study asserts promising avenues where immune cells can be trained using different odors in modulating immune cell repertoire. Such an approach can be employed as a promising means to combat infections.

“This study asserts promising avenues where immune cells can be trained using different odors in modulating immune cell repertoire.”

What was the exciting moment (eureka moment) during your research?

In the beginning, we were focused on investigating the metabolic aspect of progenitor development, and totally as an exploration, we set out to ask if perturbing GABA metabolism in blood progenitor cells affects immune responses upon immune challenge condition. To our surprise, we found that these animals could not mount the infection due to their inability to make lamellocytes. Definitely, that was the most exhilarating moment for us and gave us a compelling insight to chase for an olfaction connection.

What do you hope to do next?

My immediate goal is to investigate the role of GABA metabolism in mature blood cells, which majorly comprises of plasmatocytes in Drosophila, a macrophage counterpart in the mammalian system.

Where do you seek scientific inspiration?

I feel so fortunate to have embarked upon my doctoral research journey under the mentorship of Dr. Tina Mukherjee. Her guidance, immense support, and constant motivation have helped me to develop critical thinking and advance my scientific temperament over the years. Working in such a premier research institute enriched with a vibrant, advanced, and nurturing scientific community infuses the scientific drive to explore and learn something new each day. Reading past and new scientific discoveries in the field and discussing and sharing the thoughts with the peers always keeps me recharged with scientific interest. Since childhood, I have always been amazed and hugely inspired by India’s eminent scientist and former president Dr. A. P. J Abdul Kalam. His contribution and dedication to science have instilled a sense of pride, and his teachings will always inspire me in the scientific pursuit.

How do you intend to help Indian science improve?

Experienced as a graduate teacher in the past and mentor for lab junior students, I am convinced that young minds acted as the backbone for scientific development in any country. So inculcating the interest and curiosity in science at the early stage in schools and colleges lays the foundation for developing the scientific temperament of the nation. More outreach programs and constant engagements between the research community and youth to bring to them science beyond textbooks would go a long way. As a person with an earnest interest in teaching students, I am always keen to get involved in such ventures from time to time. While accomplishing research skills and advancement in my career ahead, I would be dedicated enough to evolving as a good teacher with the aim to contribute in creating a strong scientific cadre for the future of India.

Reference

Sukanya Madhwal, Mingyu Shin, Ankita Kapoor, Manisha Goyal, Manish K Joshi, Pirzada Mujeeb Ur Rehman, Kavan Gor, Jiwon Shim , Tina Mukherjee. Metabolic control of cellular immune-competency by odors in Drosophila. eLife 2020;9:e60376 doi: 10.7554/eLife.60376

Email: sukanyam@instem.res.in

Prof. Tina Mukherjee lab: http://tinalab.weebly.com/

Edited by: Manveen K Sethi and Govinda Raju Yedida (Volunteers, Bio Patrika)

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