Toll-Like Receptors (TLRs) in Health and Disease: An Overview

Kumar, Vijay; Barrett, James E.

doi:10.1007/164_2021_568

Cited by 22 publications

(21 citation statements)

References 127 publications

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“…Of the 13 TLRs identified in mammals ( Vijay, 2018 ), TLR1 to TLR9 are conserved between humans and mice ( Kumar and Barrett, 2022 ). TLR1, 2, 4, 5, and 6 are expressed in cell membranes.…”

Section: Role Of Tlrs In Brucella Infectionmentioning

confidence: 99%

Brucella infection and Toll-like receptors

Yu,

Gu,

Wang

et al. 2024

Front. Cell. Infect. Microbiol.

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Brucella consists of gram-negative bacteria that have the ability to invade and replicate in professional and non-professional phagocytes, and its prolonged persistence in the host leads to brucellosis, a serious zoonosis. Toll-like receptors (TLRs) are the best-known sensors of microorganisms implicated in the regulation of innate and adaptive immunity. In particular, TLRs are transmembrane proteins with a typical structure of an extracellular leucine-rich repeat (LRR) region and an intracellular Toll/interleukin-1 receptor (TIR) domain. In this review, we discuss Brucella infection and the aspects of host immune responses induced by pathogens. Furthermore, we summarize the roles of TLRs in Brucella infection, with substantial emphasis on the molecular insights into its mechanisms of action.

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“…Of the 13 TLRs identified in mammals ( Vijay, 2018 ), TLR1 to TLR9 are conserved between humans and mice ( Kumar and Barrett, 2022 ). TLR1, 2, 4, 5, and 6 are expressed in cell membranes.…”

Section: Role Of Tlrs In Brucella Infectionmentioning

confidence: 99%

Brucella infection and Toll-like receptors

Yu,

Gu,

Wang

et al. 2024

Front. Cell. Infect. Microbiol.

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“…Lipopolysaccharide (LPS) is the principal component of the outer membrane of Gram-negative bacteria, contributing significantly to the structural integrity of the bacterium and protecting it against certain forms of chemical attack ( 106 ). LPS treatment of macrophages ( 67 ), monocytes ( 68 ), and primary bone marrow-derived DCs ( 69 ) results in enhanced PD-L1 expression.…”

Section: Regulation Of Pd-1 and Pd-l1 Expressionmentioning

confidence: 99%

Role of regulation of PD-1 and PD-L1 expression in sepsis

Zhang

Yu-Jing

2023

Front. Immunol.

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Long term immunosuppression is problematic during sepsis. The PD-1 and PD-L1 immune checkpoint proteins have potent immunosuppressive functions. Recent studies have revealed several features of PD-1 and PD-L1 and their roles in sepsis. Here, we summarize the overall findings of PD-1 and PD-L1 by first reviewing the biological features of PD-1 and PD-L1 and then discussing the mechanisms that control the expression of PD-1 and PD-L1. We then review the functions of PD-1 and PD-L1 in physiological settings and further discuss PD-1 and PD-L1 in sepsis, including their involvement in several sepsis-related processes and their potential therapeutic relevance in sepsis. In general, PD-1 and PD-L1 have critical roles in sepsis, indicating that their regulation may be a potential therapeutic target for sepsis.

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“…Humans have consumed plant medicines and their resident MOCs for millennia, attributing the health benefits only to the plant and constituent phytochemicals. However, a small number of research teams have proposed that the health benefits of certain herbs may instead be due to their inactivated microbial biomass after separating the plants bioactive MAMPs from the plant itself ( 39 – 41 ). This theory aligns with the broader field of microbiomic science and the simple logic that the immune system responds aggressively not to phytochemicals or drugs but to the presence of foreign antigenic microorganism debris (MAMPs), the basis for vaccine and adjuvant development.…”

Section: Plant Medicine: the Plant Microbiomementioning

confidence: 99%

Plants against cancer: the immune-boosting herbal microbiome: not of the plant, but in the plant. Basic concepts, introduction, and future resource for vaccine adjuvant discovery

Mazzio,

Barnes,

Badisa

et al. 2023

Front. Oncol.

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The presence of microorganism communities (MOCs) comprised of bacteria, fungi, archaea, algae, protozoa, viruses, and the like, are ubiquitous in all living tissue, including plant and animal. MOCs play a significant role in establishing innate and acquired immunity, thereby influencing susceptibility and resistance to disease. This understanding has fostered substantial advancements in several fields such as agriculture, food science/safety, and the development of vaccines/adjuvants, which rely on administering inactivated-attenuated MOC pathogens. Historical evidence dating back to the 1800s, including reports by Drs Busch, Coley, and Fehleisen, suggested that acute febrile infection in response to “specific microbes” could trigger spontaneous tumor remission in humans. This discovery led to the purposeful administration of the same attenuated strains, known as “Coley’s toxin,” marking the onset of the first microbial (pathogen) associated molecular pattern (MAMPs or PAMPs)-based tumor immunotherapy, used clinically for over four decades. Today, these same MAMPS are consumed orally by billions of consumers around the globe, through “specific” mediums (immune boosting “herbal supplements”) as carriers of highly concentrated MOCs accrued in roots, barks, hulls, sea algae, and seeds. The American Herbal Products Association (AHPA) mandates microbial reduction in botanical product processing but does not necessitate the removal of dead MAMP laden microbial debris, which we ingest. Moreover, while existing research has focused on the immune-modulating role of plant phytochemicals, the actual immune-boosting properties might instead reside solely in the plant’s MOC MAMP laden biomass. This assertion is logical, considering that antigenic immune-provoking epitopes, not phytochemicals, are known to stimulate immune response. This review explores a neglected area of research regarding the immune-boosting effects of the herbal microbiome – a presence which is indirectly corroborated by various peripheral fields of study and poses a fundamental question: Given that food safety focuses on the elimination of harmful pathogens and crop science acknowledges the existence of plant microbiomes, what precisely are the immune effects of ingesting MAMPs of diverse structural composition and concentration, and where are these distributed in our botanicals? We will discuss the topic of concentrated edible MAMPs as acid and thermally stable motifs found in specific herbs and how these would activate cognate pattern recognition receptors (PPRs) in the upper gut-associated lymphoid tissue (GALT), including Peyer’s patches and the lamina propria, to boost antibody titers, CD8+ and CD4+ T cells, NK activity, hematopoiesis, and facilitating M2 to M1 macrophage phenotype transition in a similar manner as vaccines. This new knowledge could pave the way for developing bioreactor-grown/heat-inactivated MOC therapies to boost human immunity against infections and improve tumor surveillance.

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Toll-Like Receptors (TLRs) in Health and Disease: An Overview

Cited by 22 publications

References 127 publications

Brucella infection and Toll-like receptors

Brucella infection and Toll-like receptors

Role of regulation of PD-1 and PD-L1 expression in sepsis

Plants against cancer: the immune-boosting herbal microbiome: not of the plant, but in the plant. Basic concepts, introduction, and future resource for vaccine adjuvant discovery

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