Association of ficolin‐1 and ficolin‐3 gene variation and pulmonary tuberculosis susceptibility in a Chinese population

Li, Ye; You, En-Qing; Lin, Weihong; Liu, Xiaoning; Shen, De-Pei; Zhang, Xinli; Ma, Ding; Li, Hong‐Miao

doi:10.1002/jcla.23732

Cited by 2 publications

(1 citation statement)

References 33 publications

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“…Two promoter variants in CD209 are associated with TB in multiple African populations (187)(188)(189), South Asians (190) and Brazilians (191). Other PRRs, such as ficolins, have been evaluated for association with TB (192,193), while studies with genes encoding proteins of the complement and PRRs for the RIG-1 family have not yet been reported.…”

Section: Prr Diversity In Humans and Outcomes Of Mtb Infectionmentioning

confidence: 99%

Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis

et al. 2021

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Human genetic control is thought to affect a considerable part of the outcome of infection with Mycobacterium tuberculosis (Mtb). Most of us deal with the pathogen by containment (associated with clinical “latency”) or sterilization, but tragically millions each year do not. After decades of studies on host genetic susceptibility to Mtb infection, genetic variation has been discovered to play a role in tuberculous immunoreactivity and tuberculosis (TB) disease. Genes encoding pattern recognition receptors (PRRs) enable a consistent, molecularly direct interaction between humans and Mtb which suggests the potential for co-evolution. In this review, we explore the roles ascribed to PRRs during Mtb infection and ask whether such a longstanding and intimate interface between our immune system and this pathogen plays a critical role in determining the outcome of Mtb infection. The scientific evidence to date suggests that PRR variation is clearly implicated in altered immunity to Mtb but has a more subtle role in limiting the pathogen and pathogenesis. In contrast to ‘effectors’ like IFN-γ, IL-12, Nitric Oxide and TNF that are critical for Mtb control, ‘sensors’ like PRRs are less critical for the outcome of Mtb infection. This is potentially due to redundancy of the numerous PRRs in the innate arsenal, such that Mtb rarely goes unnoticed. Genetic association studies investigating PRRs during Mtb infection should therefore be designed to investigate endophenotypes of infection – such as immunological or clinical variation – rather than just TB disease, if we hope to understand the molecular interface between innate immunity and Mtb.

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Section: Prr Diversity In Humans and Outcomes Of Mtb Infectionmentioning

confidence: 99%

Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis

et al. 2021

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Mycobacterium tuberculosis Affects Protein and Lipid Content of Circulating Exosomes in Infected Patients Depending on Tuberculosis Disease State

et al. 2022

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Tuberculosis (TB), which is caused by the bacterium Mycobacterium tuberculosis (Mtb), is still one of the deadliest infectious diseases. Understanding how the host and pathogen interact in active TB will have a significant impact on global TB control efforts. Exosomes are increasingly recognized as a means of cell-to-cell contact and exchange of soluble mediators. In the case of TB, exosomes are released from the bacillus and infected cells. In the present study, a comprehensive lipidomics and proteomics analysis of size exclusion chromatography-isolated plasma-derived exosomes from patients with TB lymphadenitis (TBL) and treated as well as untreated pulmonary TB (PTB) was performed to elucidate the possibility to utilize exosomes in diagnostics and knowledge building. According to our findings, exosome-derived lipids and proteins originate from both the host and Mtb in the plasma of active TB patients. Exosomes from all patients are mostly composed of sphingomyelins (SM), phosphatidylcholines, phosphatidylinositols, free fatty acids, triacylglycerols (TAG), and cholesterylesters. Relative proportions of, e.g., SMs and TAGs, vary depending on the disease or treatment state and could be linked to Mtb pathogenesis and dormancy. We identified three proteins of Mtb origin: DNA-directed RNA polymerase subunit beta (RpoC), Diacyglycerol O-acyltransferase (Rv2285), and Formate hydrogenase (HycE), the latter of which was discovered to be differently expressed in TBL patients. Furthermore, we discovered that Mtb infection alters the host protein composition of circulating exosomes, significantly affecting a total of 37 proteins. All TB patients had low levels of apolipoproteins, as well as the antibacterial proteins cathelicidin, Scavenger Receptor Cysteine Rich Family Member (SSC5D), and Ficolin 3 (FCN3). When compared to healthy controls, the protein profiles of PTB and TBL were substantially linked, with 14 proteins being co-regulated. However, adhesion proteins (integrins, Intercellular adhesion molecule 2 (ICAM2), CD151, Proteoglycan 4 (PRG4)) were shown to be more prevalent in PTB patients, while immunoglobulins, Complement component 1r (C1R), and Glutamate receptor-interacting protein 1 (GRIP1) were found to be more abundant in TBL patients, respectively. This study could confirm findings from previous reports and uncover novel molecular profiles not previously in focus of TB research. However, we applied a minimally invasive sampling and analysis of circulating exosomes in TB patients. Based on the findings given here, future studies into host–pathogen interactions could pave the way for the development of new vaccines and therapies.

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Association of ficolin‐1 and ficolin‐3 gene variation and pulmonary tuberculosis susceptibility in a Chinese population

Cited by 2 publications

References 33 publications

Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis

Underwhelming or Misunderstood? Genetic Variability of Pattern Recognition Receptors in Immune Responses and Resistance to Mycobacterium tuberculosis

Mycobacterium tuberculosis Affects Protein and Lipid Content of Circulating Exosomes in Infected Patients Depending on Tuberculosis Disease State

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