Modulation of Macrophage Signaling Pathways during Bacterial Infections

About this Research Topic

Background

Intracellular pathogenic bacteria cause some of the most life-threatening diseases. These
pathogens successfully evade host immune response and establish persistent infection. Some of the most deadly bacterial pathogens include Salmonella enterica, Listeria monocytogenes and Mycobacterium Tuberculosis (MTB). Tuberculosis (TB), one of the oldest known human diseases, is the leading cause of death from a single infectious agent (WHO, 2017). People with impaired immune functions are at a heightened risk of developing active disease, making TB co-infection a leading cause of death among people with HIV.

Despite the availability of improved diagnostics and treatment options intracellular bacterial diseases continue to pose a major public health challenge worldwide. Emergence of drug resistance pathogens, such as meticillin-resistant Staphylococcus aureus, multi-drug resistant (MDR) Mtb and others, further dampen the prospect of eradicating these infectious diseases. A greater understanding of the mechanisms of host-pathogen interactions and rewiring of host signaling pathways during infection will aid in the development of novel Host-directed therapies (HDT) and therapeutic targets.

Macrophages are the first innate immune responders during bacterial infection and play a central role in mounting an effective host immune response. Macrophages are equipped with several effector mechanisms to recognize and kill the invading bacteria, yet pathogens have evolved strategies to evade immune responses and remain viable within the infected cells. Upon bacterial exposure, macrophages recognize and uptake bacteria through various pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), Nod-like receptors (NLRs), Mannose receptors (MRs) and C-type lectin receptors (CLRs) and activate coordinated signaling pathways which in turn induce expressions of regulatory genes, cytokines, chemokines and trigger immune defense functions such as bacterial phagocytosis, autophagy, apoptosis, antigen processing and presentation.

The bacterium, on the other hand, manipulates macrophage signaling pathways and interferes with host protective responses to survive and establish infection. More work is needed to fully understand the complexity of intracellular infections and host-pathogen interactions. Identifying host factors that are exploited by pathogens will help develop targets for HDT.
This research topic welcomes articles focusing on the function and/or mechanisms of signaling pathways that are activated/regulated in macrophages during bacterial infections.

Researchers may contribute Reviews, Mini-Reviews, Brief Research Reports or Original Research articles.

Keywords: Pattern Recognition Receptors (PRRs), Innate Immune Response, Intracellular Pathogens, Myeloid Cells, Host-directed Therapy (HDT)

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