scholarly journals Infection-induced 5′-half molecules of tRNAHisGUG activate Toll-like receptor 7

PLoS Biology ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. e3000982
Author(s):  
Kamlesh Pawar ◽  
Megumi Shigematsu ◽  
Soroush Sharbati ◽  
Yohei Kirino
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Human Monocyte ◽  
Mycobacterial Infection ◽  
Innate Immune ◽  
Mirna Sequence ◽  
Sequence Identification ◽  
Trna Half ◽  
Rna Ligands ◽  
Trna Halves

Toll-like receptors (TLRs) play a crucial role in the innate immune response. Although endosomal TLR7 recognizes single-stranded RNAs, their endogenous RNA ligands have not been fully explored. Here, we report 5′-tRNA half molecules as abundant activators of TLR7. Mycobacterial infection and accompanying surface TLR activation up-regulate the expression of 5′-tRNA half molecules in human monocyte-derived macrophages (HMDMs). The abundant accumulation of 5′-tRNA halves also occur in HMDM-secreted extracellular vehicles (EVs); the abundance of EV-5′-tRNAHisGUG half molecules is >200-fold higher than that of the most abundant EV-microRNA (miRNA). Sequence identification of the 5′-tRNA halves using cP-RNA-seq revealed abundant and selective packaging of specific 5′-tRNA half species into EVs. The EV-5′-tRNAHisGUG half was experimentally demonstrated to be delivered into endosomes in recipient cells and to activate endosomal TLR7. Up-regulation of the 5′-tRNA half molecules was also observed in the plasma of patients infected with Mycobacterium tuberculosis. These results unveil a novel tRNA-engaged pathway in the innate immune response and assign the role of “immune activators” to 5′-tRNA half molecules.

scholarly journals Defining the Immune Responses for SARS-CoV-2-Human Macrophage Interactions

2021 ◽  
Author(s):  
Mai Mostafa ◽  
Pravin Yeapuri ◽  
Jatin Machhi ◽  
Katherine Olson ◽  
Farah Shahjin ◽  
...  
Keyword(s):  
Immune Response ◽  
Viral Infection ◽  
Innate Immune Response ◽  
Human Monocyte ◽  
Innate Immune ◽  
Mononuclear Phagocytes ◽  
Human Macrophage ◽  
Type I ◽  
Innate Immune Signaling ◽  
Organ Tissue

Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end organ malfunctions. All follow an abortive viral infection. To elucidate SARS-CoV-2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding consequent end-organ tissue damage.

scholarly journals Mycobacterial infection induces a specific human innate immune response

2015 ◽  
Author(s):  
John D Blischak ◽  
Ludovic Tailleux ◽  
Amy Mitrano ◽  
Luis B Barreiro ◽  
Yoav Gilad
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Innate Immune Response ◽  
Transcriptional Response ◽  
Adaptive Immune System ◽  
Mycobacterial Infection ◽  
Innate Immune ◽  
Pathogen Infection ◽  
General Response ◽  
Candidate Loci

The innate immune system provides the first response to pathogen infection and orchestrates the activation of the adaptive immune system. Though a large component of the innate immune response is common to all infections, pathogen-specific responses have been documented as well. The innate immune response is thought to be especially critical for fighting infection with Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis (TB). While TB can be deadly, only 5-10% of individuals infected with MTB develop active disease. The risk for disease susceptibility is, at least partly, heritable. Studies of inter-individual variation in the innate immune response to MTB infection may therefore shed light on the genetic basis for variation in susceptibility to TB. Yet, to date, we still do not know which properties of the innate immune response are specific to MTB infection and which represent a general response to pathogen infection. To begin addressing this gap, we infected macrophages with eight different bacteria, including different MTB strains and related mycobacteria, and studied the transcriptional response to infection. Although the ensued gene regulatory responses were largely consistent across the bacterial infection treatments, we were able to identify a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. Genetic variants that are associated with regulatory differences in these genes should be considered candidate loci for explaining inter-individual susceptibility TB.

scholarly journals Defining the Innate Immune Responses for SARS-CoV-2-Human Macrophage Interactions

2021 ◽  
Vol 12 ◽  
Author(s):  
Mai M. Abdelmoaty ◽  
Pravin Yeapuri ◽  
Jatin Machhi ◽  
Katherine E. Olson ◽  
Farah Shahjin ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Human Monocyte ◽  
Innate Immune ◽  
Mononuclear Phagocytes ◽  
Human Macrophage ◽  
Type I ◽  
Innate Immune Signaling ◽  
Life Threatening ◽  
Organ Tissue

Host innate immune response follows severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and it is the driver of the acute respiratory distress syndrome (ARDS) amongst other inflammatory end-organ morbidities. Such life-threatening coronavirus disease 2019 (COVID-19) is heralded by virus-induced activation of mononuclear phagocytes (MPs; monocytes, macrophages, and dendritic cells). MPs play substantial roles in aberrant immune secretory activities affecting profound systemic inflammation and end-organ malfunctions. All follow the presence of persistent viral components and virions without evidence of viral replication. To elucidate SARS-CoV-2-MP interactions we investigated transcriptomic and proteomic profiles of human monocyte-derived macrophages. While expression of the SARS-CoV-2 receptor, the angiotensin-converting enzyme 2, paralleled monocyte-macrophage differentiation, it failed to affect productive viral infection. In contrast, simple macrophage viral exposure led to robust pro-inflammatory cytokine and chemokine expression but attenuated type I interferon (IFN) activity. Both paralleled dysregulation of innate immune signaling pathways, specifically those linked to IFN. We conclude that the SARS-CoV-2-infected host mounts a robust innate immune response characterized by a pro-inflammatory storm heralding end-organ tissue damage.

scholarly journals Expression of Cathelicidin LL-37 during Mycobacterium tuberculosis Infection in Human Alveolar Macrophages, Monocytes, Neutrophils, and Epithelial Cells

2007 ◽  
Vol 76 (3) ◽  
pp. 935-941 ◽  
Author(s):  
Bruno Rivas-Santiago ◽  
Rogelio Hernandez-Pando ◽  
Claudia Carranza ◽  
Esmeralda Juarez ◽  
Juan Leon Contreras ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Epithelial Cells ◽  
Innate Immune Response ◽  
Alveolar Macrophages ◽  
Mycobacterial Infection ◽  
Innate Immune ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection ◽  
Peptide Expression

ABSTRACT The innate immune response in human tuberculosis is not completely understood. To improve our knowledge regarding the role of cathelicidin hCAP-18/LL37 in the innate immune response to tuberculosis infection, we used immunohistochemistry, immunoelectron microscopy, and gene expression to study the induction and production of the antimicrobial peptide in A549 epithelial cells, alveolar macrophages (AM), neutrophils, and monocyte-derived macrophages (MDM) after infection with Mycobacterium tuberculosis. We demonstrated that mycobacterial infection induced the expression and production of LL-37 in all cells studied, with AM being the most efficient. We did not detect peptide expression in tuberculous granulomas, suggesting that LL-37 participates only during early infection. Through the study of Toll-like receptors (TLR) in MDM, we showed that LL-37 can be induced by stimulation through TLR-2, TLR-4, and TLR-9. This last TLR was strongly stimulated by M. tuberculosis DNA. We concluded that LL-37 may have an important role in the innate immune response against M. tuberculosis.

scholarly journals Mycobacterial infection induces a specific human innate immune response

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
John D. Blischak ◽  
Ludovic Tailleux ◽  
Amy Mitrano ◽  
Luis B. Barreiro ◽  
Yoav Gilad
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Mycobacterial Infection ◽  
Innate Immune

scholarly journals Bacillus anthracis Capsule Activates Caspase-1 and Induces Interleukin-1β Release from Differentiated THP-1 and Human Monocyte-Derived Dendritic Cells

2009 ◽  
Vol 78 (1) ◽  
pp. 387-392 ◽  
Author(s):  
Min-Hee Cho ◽  
Hae-Jeong Ahn ◽  
Hyun-Joon Ha ◽  
Jungchan Park ◽  
Jeong-Hoon Chun ◽  
...  
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Bacillus Anthracis ◽  
Innate Immune Response ◽  
Human Monocyte ◽  
Innate Immune ◽  
Interleukin 1Β ◽  
Dependent Manner ◽  
Caspase 1 ◽  
Extracellular Release

ABSTRACT The poly-γ-d-glutamic acid (PGA) capsule is one of the major virulence factors of Bacillus anthracis, which causes a highly lethal infection. The antiphagocytic PGA capsule disguises the bacilli from immune surveillance and allows unimpeded growth of bacilli in the host. Recently, efforts have been made to include PGA as a component of anthrax vaccine; however, the innate immune response of PGA itself has been poorly investigated. In this study, we characterized the innate immune response elicited by PGA in the human monocytic cell line THP-1, which was differentiated into macrophages with phorbol 12-myristate 13-acetate (PMA) and human monocyte-derived dendritic cells (hMoDCs). PGA capsules were isolated from the culture supernatant of either the pXO1-cured strain of B. anthracis H9401 or B. licheniformis ATCC 9945a. PGA treatment of differentiated THP-1 cells and hMoDCs led to the specific extracellular release of interleukin-1β (IL-1β) in a dose-dependent manner. Evaluation of IL-1β processing by Western blotting revealed that cleaved IL-1β increased in THP-1 cells and hMoDCs after PGA treatment. Enhanced processing of IL-1β directly correlated with increased activation of its upstream regulator, caspase-1, also known as IL-1β-converting enzyme (ICE). The extracellular release of IL-1β in response to PGA was ICE dependent, since the administration of an ICE inhibitor prior to PGA treatment blocked induction of IL-1β. These results demonstrate that B. anthracis PGA elicits IL-1β production through activation of ICE in PMA-differentiated THP-1 cells and hMoDCs, suggesting the potential for PGA as a therapeutic target for anthrax.

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