Mycobacterial infection induces a specific human innate immune response

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.

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

PLoS Biology ◽

10.1371/journal.pbio.3000982 ◽

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.

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

Infection and Immunity ◽

10.1128/iai.01218-07 ◽

2007 ◽

Vol 76 (3) ◽

pp. 935-941 ◽

Cited By ~ 130

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.

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Coupling of Petri Net Models of the Mycobacterial Infection Process and Innate Immune Response

Computation ◽

10.3390/computation3020150 ◽

2015 ◽

Vol 3 (2) ◽

pp. 150-176 ◽

Cited By ~ 5

Author(s):

Rafael Carvalho ◽

Jeroen van den Heuvel ◽

Jetty Kleijn ◽

Fons Verbeek

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Petri Net ◽

Mycobacterial Infection ◽

Infection Process ◽

Innate Immune

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Oral Immune Activation by Disgust and Disease-Related Pictures

Journal of Psychophysiology ◽

10.1027/0269-8803/a000143 ◽

2015 ◽

Vol 29 (3) ◽

pp. 119-129 ◽

Cited By ~ 4

Author(s):

Richard J. Stevenson ◽

Deborah Hodgson ◽

Megan J. Oaten ◽

Luba Sominsky ◽

Mehmet Mahmut ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Innate Immune Response ◽

Negative Control ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Markers ◽

Before And After ◽

Secondary Analyses ◽

Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

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