Cellular Immune Response and Escape Mechanisms of Intracellular Parasites

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Background

Infectious parasitic diseases are among the biggest causes of death in the world. Infections of the lower respiratory tract and diarrheal diseases are among the ten leading causes of death in 2019. According to the World Health Organization (WHO, 2019), parasitic diseases are the most common diseases in the world, affecting about 50% of the world's population. These infections are responsible for relevant negative health consequences for adults and children. Innate and adaptive immune responses protect against these infections, and their magnitude and effectiveness are strongly influenced by host and parasite factors. Among the factors influencing the immune response related to hosts are immunocompetence, health status, eating habits and sedentary or active lifestyle. As for those that affect the parasites, we can mention their virulence, their habitat, and their escape mechanisms. Depending on the type of parasitic infection, the stimulated immune response may be predominantly humoral, such as in the case of infections by helminths and extracellular parasites, or predominantly cellular, aiming to reach intracellular parasites. In general, the cellular immune response initiates by stimulating T helper lymphocytes in a microenvironment with the cytokine IL-12 and antigen-presenting cells such as macrophages or dendritic cells. This is the case of parasites such as Trypanosoma cruzi, Leishmania spp and Toxoplasma gondii, and the bacteria that cause tuberculosis, leprosy, and viral infections. Understanding the effector mechanisms of the immune response against intracellular parasites and how to prevent these microorganisms from evading the immune responses is essential to help control and prevent these diseases. Moreover, understanding the host immune response to infections can help develop new and more effective therapies with less toxicity than the existing ones, in addition to those aimed at producing effective vaccines to control these diseases.

Intracellular parasites develop different strategies to subvert the defense mechanisms used by host cells. They can modulate the host's innate and adaptive immune pathways and cellular metabolism to establish a niche that contributes to their survival and replication. Several escape mechanisms have been used by different parasites. Some of them include: 1) Parasites may secrete substances that can impair the activity of T cells and macrophages, 2) they can modulate the endosomal maturation and survival in vacuoles with controlled pH inside host cells, 3) they can escape from the cytoplasm or block the fusion of phagosomes and lysosomes and, 4) they may modulate the metabolic status of the cell favoring its survival.

In this research topic, we intend to focus on discoveries of mechanisms associated with the cellular immune response to intracellular including parasites' mechanisms of evasion of intracellular host defenses. We will publish studies on modulators of the host cellular immune response, the metabolic control of host cells by parasites, innate and immune pathways subverted by the parasites, and strategies to develop new treatments or prophylaxis against diseases. Furthermore, we will consider studies on the ability of pathogens to modulate the cellular environment and phenotypes, including autocrine and paracrine signaling between cells. We are interested in shedding new light on the mechanisms that modulate the cellular immune response to intracellular parasites and the evasion mechanisms used by intracellular pathogens. Contributions covering the role of parasites in modulating host cell death pathways are also of interest.

We welcome authors to submit original research, review, and mini-review articles covering, but not limited to the following topics:

1. Studies aiming to understand the modulation of cellular immunity from mammalian hosts.
2. Studies aiming to understand the modulation of host cell metabolism by intracellular pathogens.
3. Studies emphasizing the modulation of both innate and adaptive immune systems by intracellular parasites.
4. The modulation of host cell death pathways by different intracellular pathogens, including bacteria, fungi, virus and protozoans.
5. Mechanisms of evasion used by the pathogens to maintain their survival and replication inside host cells.
6. New therapeutics or prophylactics that focus on strategies to impair the parasite's escape from the immune system.

Keywords: Innate and adaptive immune response, cellular metabolism, cell death pathways, evasion mechanisms, host microbicidal pathways

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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