Hridayesh Prakash

By Mishi Wasson, Sonia Kapoor, Manoj Garg, Sandhya Singh and Hridayesh Prakash

Macrophages are the special cells of the immune system and play both immunological and physiological role. One of the peculiar characteristics of macrophages is that they are double-edged and highly plastic component of immune system. Due to this characteristic, they are responsible for both progressions as well control of a variety of inflammatory, infectious and metabolic diseases and cancer. These are found in the body in three major phenotypes, which are known as M0 (also known as naïve); M1 (classically activated macrophages); and/or M2 (alternatively activated macrophages) at normal physiological conditions. We have been exploring macrophages in context of bacterial infection and previously demonstrated that M2 polarization of M1 effector alveolar macrophages during chronic/persistent Chlamydia pneumonia, Mycobacterium tuberculosis and Helicobacter pylori pathogens are decisive for the infection induced cancer development in host. Since chronic infection with these pathogens has been associated with adenocarcinoma, therefore, we feel that disruption of macrophage plasticity plays crucial role in the host for the development of cancer. On the basis of this, we propose that in such pathological conditions, management of M1/M2 imbalance is paramount for minimizing the risk of developing cancer by chronic and persistent infection.

Part of the book: Macrophage Activation

By Lovlesh Thakur, Nadeem Akhtar, Aklank Jain, Hridayesh Parkash and Manju Jain

Parasitic infections are the major threat prevalent in tropical and subtropical regions throughout the world. Different parasitic infections take a huge toll on mortality and morbidity at global level. Different parasites invade the host system, multiply inside host cells of their choice and sabotage defense mechanisms to overpower the host. T-cell immunity is majorly affected in different parasitic diseases such that the peripheral T-cell immune response is altered along with lesser explored thymic changes. Direct and/or indirect effect of parasitic infection leads to alterations in T-cell development, differentiation and activation resulting in deregulated T-cell immune mechanisms. Cytokines of interferon family play a significant role in determining the disease outcome and severity. Therefore, in this chapter, we here provide a detailed overview of the functional role played by IFNs during parasitic diseases in terms of their influence on peripheral T-cell activation and tolerance along with lesser explored impact on developing T cells in the thymus with altered microenvironmental niches.

Part of the book: Innate Immunity in Health and Disease

By Vishwas Tripathi, Amaresh Mishra, Yamini Pathak, Aklank Jain and Hridayesh Prakash

Fibromyalgia (FM) or Fibromyalgia Syndrome (FMS) is a neurodegenerative disorder causing musculoskeletal pain, tenderness, stiffness, fatigue, and sleep disorder in the body. It is one of the most common chronic pain conditions, affecting about 6% of the world population. Being refractory, till date, no specific treatment of this disease is available. Accumulating evidences over the last few decades indicate that proinflammatory macrophages, cytokines, & chemokines as the key players in this disease. Recent findings suggest activation of Microglial cells and associated pro-inflammatory signals as one of the major causes of chronic pain in patients suffering from fibromyalgia. Increased density of iNOs/CD68+ M1 effector macrophages has been associated with neuropathic pain models. In light of this, depletion of these pro-inflammatory macrophages has been shown to reduce sensitivity to neuropathic pain. On the other hand, modulating pattern of AGEs (Advanced Glycation End-Products) can also contribute to inactivation of macrophages. These findings strongly suggest that macrophages are critical in both inflammatory and neuropathic pain. Therefore, this chapter highlights the impact of macrophage plasticity in various immunopathological aspects of fibromyalgia.

Part of the book: Macrophages

By Apoorv Sharma, Abhishek K. Singh, Vijay Kumar and Hridayesh Prakash

The interplay between the central nervous system (CNS) and the enteric nervous system (ENS) constitutes the gut-brain axis. This represents a dynamic and bidirectional network of signaling pathways involving the vagus nerve, the immune system, and the molecules released by various microorganisms thriving in our gut. Since humans and bacteria have evolved together and learned to live together in a symbiotic relationship, which is decisive for physio/immune homeostasis of the body. Disruption in this (also known as dysbiosis) is associated with various pathological consequences including several neurological disorders. Out of several pathways that are associated with neurological manifestation, the inflammasome pathway is associated with the progression of multiple sclerosis, Alzheimer’s, and Parkinson’s disease, depression, schizophrenia, and autism. A growing body of evidence now suggests a reciprocal influence of microbiota and inflammasome activation in the brain. In this chapter, we discuss the cross talk between human gut microbiota and the key immunological signaling processes and their role in CNS development and neurological diseases.

Part of the book: Basic and Clinical Aspects of Interferon Gamma