scholarly journals Mycoketide: A CD1c-Presented Antigen with Important Implications in Mycobacterial Infection

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Isamu Matsunaga ◽  
Masahiko Sugita
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Host Defense ◽  
Biosynthetic Pathway ◽  
Mycobacterial Infection ◽  
Acquired Immunity ◽  
Human Group ◽  
Unique Role ◽  
Lipid Antigens ◽  
Group 1

Mycobacterium tuberculosisand related mycobacteria species are unique in that the acid-fast bacilli possess a highly lipid-rich cell wall that not simply confers resistance to treatment with acid alcohol, but also controls their survival and virulence. It has recently been established that a fraction of the cell wall lipid components of mycobacteria can function as antigens targeted by the acquired immunity of the host. Human group 1 CD1 molecules (CD1a, CD1b, and CD1c) bind a pool of lipid antigens expressed by mycobacteria and present them to specific T cells, thereby mediating an effective pathway for host defense against tuberculosis. The contrasting and mutually complementary functions of CD1a and CD1b molecules in terms of the repertoire of antigens they bind have been well appreciated, but it remains to be established how CD1c may play a unique role. Nevertheless, recent advances in our understanding of the CD1c structure as well as the biosynthetic pathway of a CD1c-presented antigen, mannose-1, β-phosphomycoketide, expressed by pathogenic mycobacteria now unravel a new aspect of the group 1 CD1 biology that has not been appreciated in previous studies of CD1a and CD1b molecules.

scholarly journals Mycolic acid-specific T cells protect against Mycobacterium tuberculosis infection in a humanized transgenic mouse model

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Jie Zhao ◽  
Sarah Siddiqui ◽  
Shaobin Shang ◽  
Yao Bian ◽  
Sreya Bagchi ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Protective Immunity ◽  
Mycolic Acid ◽  
Human Group ◽  
Specific Group ◽  
Mycobacterium Tuberculosis Infection ◽  
Lipid Antigens ◽  
Aerosol Infection ◽  
Group 1

Group 1 CD1 molecules, CD1a, CD1b and CD1c, present lipid antigens from Mycobacterium tuberculosis (Mtb) to T cells. Mtb lipid-specific group 1 CD1-restricted T cells have been detected in Mtb-infected individuals. However, their role in protective immunity against Mtb remains unclear due to the absence of group 1 CD1 expression in mice. To overcome the challenge, we generated mice that expressed human group 1 CD1 molecules (hCD1Tg) and a CD1b-restricted, mycolic-acid specific TCR (DN1Tg). Using DN1Tg/hCD1Tg mice, we found that activation of DN1 T cells was initiated in the mediastinal lymph nodes and showed faster kinetics compared to Mtb Ag85B-specific CD4+ T cells after aerosol infection with Mtb. Additionally, activated DN1 T cells exhibited polyfunctional characteristics, accumulated in lung granulomas, and protected against Mtb infection. Therefore, our findings highlight the vaccination potential of targeting group 1 CD1-restricted lipid-specific T cells against Mtb infection.

Mycobacterial infection other than tuberculosis

2018 ◽  
Author(s):  
Stephen Aston ◽  
Geraint Davies ◽  
Nick Beeching
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Causative Agent ◽  
Mycobacterium Leprae ◽  
Mycobacterial Infection

Mycobacteria are aerobic bacilli with a lipid-rich cell wall and are widespread both in the environment and in animals. Many species within the genus cause disease in humans, most notably those of the Mycobacterium tuberculosis complex, which cause tuberculosis, and Mycobacterium leprae, the causative agent of leprosy. Several other species, termed non-tuberculous mycobacteria, can cause chronic cutaneous, pulmonary, and disseminated infections. This chapter will briefly review infection with non-tuberculous mycobacteria and Mycobacterium leprae.

scholarly journals A Microbiological, Toxicological, and Biochemical Study of the Effects of Fucoxanthin, a Marine Carotenoid, on Mycobacterium tuberculosis and the Enzymes Implicated in Its Cell Wall: A Link Between Mycobacterial Infection and Autoimmune Diseases

Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 641 ◽  
Author(s):  
Miroslava Šudomová ◽  
Mohammad Shariati ◽  
Javier Echeverría ◽  
Ioana Berindan-Neagoe ◽  
Seyed Nabavi ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Autoimmune Diseases ◽  
Drug Targets ◽  
Bacterial Infections ◽  
Animal Studies ◽  
Biochemical Study ◽  
Mycobacterial Infection ◽  
Susceptible Host ◽  
Standard Drug

This study explored the antitubercular properties of fucoxanthin, a marine carotenoid, against clinical isolates of Mycobacterium tuberculosis (Mtb). Two vital enzymes involved in Mtb cell wall biosynthesis, UDP-galactopyranose mutase (UGM) and arylamine-N-acetyltransferase (TBNAT), were selected as drug targets to reveal the mechanism underlying the antitubercular effect of fucoxanthin. The obtained results showed that fucoxanthin showed a clear bacteriostatic action against the all Mtb strains tested, with minimum inhibitory concentrations (MIC) ranging from 2.8 to 4.1 µM, along with a good degree of selectivity index (ranging from 6.1 to 8.9) based on cellular toxicity evaluation compared with standard drug isoniazid (INH). The potent inhibitory actions of fucoxanthin and standard uridine-5’-diphosphate against UGM were recorded to be 98.2% and 99.2%, respectively. TBNAT was potently inactivated by fucoxanthin (half maximal inhibitory concentration (IC50) = 4.8 µM; 99.1% inhibition) as compared to INH (IC50 = 5.9 µM; 97.4% inhibition). Further, molecular docking approaches were achieved to endorse and rationalize the biological findings along with envisaging structure-activity relationships. Since the clinical evidence of the last decade has confirmed the correlation between bacterial infections and autoimmune diseases, in this study we have discussed the linkage between infection with Mtb and autoimmune diseases based on previous clinical observations and animal studies. In conclusion, we propose that fucoxanthin could demonstrate great therapeutic value for the treatment of tuberculosis by acting on multiple targets through a bacteriostatic effect as well as by inhibiting UGM and TBNAT. Such outcomes may lead to avoiding or decreasing the susceptibility to autoimmune diseases associated with Mtb infection in a genetically susceptible host.

scholarly journals CD1-restricted adaptive immune responses to Mycobacteria in human group 1 CD1 transgenic mice

2009 ◽  
Vol 206 (11) ◽  
pp. 2497-2509 ◽  
Author(s):  
Kyrie Felio ◽  
Hanh Nguyen ◽  
Christopher C. Dascher ◽  
Hak-Jong Choi ◽  
Sha Li ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Small Animal ◽  
Mycobacterial Infection ◽  
Cell Receptor ◽  
Human Group ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Group 1

Group 1 CD1 (CD1a, CD1b, and CD1c)–restricted T cells recognize mycobacterial lipid antigens and are found at higher frequencies in Mycobacterium tuberculosis (Mtb)–infected individuals. However, their role and dynamics during infection remain unknown because of the lack of a suitable small animal model. We have generated human group 1 CD1 transgenic (hCD1Tg) mice that express all three human group 1 CD1 isoforms and support the development of group 1 CD1–restricted T cells with diverse T cell receptor usage. Both mycobacterial infection and immunization with Mtb lipids elicit group 1 CD1–restricted Mtb lipid–specific T cell responses in hCD1Tg mice. In contrast to CD1d-restricted NKT cells, which rapidly respond to initial stimulation but exhibit anergy upon reexposure, group 1 CD1–restricted T cells exhibit delayed primary responses and more rapid secondary responses, similar to conventional T cells. Collectively, our data demonstrate that group 1 CD1–restricted T cells participate in adaptive immune responses upon mycobacterial infection and could serve as targets for the development of novel Mtb vaccines.

scholarly journals Mycobacterium tuberculosis evasion of Guanylate Binding Protein-mediated host defense in mice requires the ESX1 secretion system

2020 ◽  
Author(s):  
Andrew J. Olive ◽  
Clare M. Smith ◽  
Christina E. Baer ◽  
Jörn Coers ◽  
Christopher M. Sassetti
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Host Defense ◽  
Genetic Interaction ◽  
Mycobacterial Infection ◽  
Secretion System ◽  
Immune Defense ◽  
Chromosome 3 ◽  
Intracellular Pathogens ◽  
Potent Inducer ◽  
Defense Proteins

AbstractCell-intrinsic immune mechanisms control intracellular pathogens that infect eukaryotes. The intracellular pathogen Mycobacterium tuberculosis (Mtb) evolved to withstand cell-autonomous immunity to cause persistent infections and disease. A potent inducer of cell-autonomous immunity is the lymphocyte-derived cytokine IFNγ. While the production of IFNγ by T cells is essential to protect against Mtb, it is not capable of fully eradicating Mtb infection. This suggests that Mtb evades a subset of IFNγ-mediated antimicrobial responses, yet what mechanisms Mtb resists remains unclear. The IFNγ-inducible Guanylate binding proteins (GBPs) are key host defense proteins able to control infections with intracellular pathogens. GBPs were previously shown to directly restrict Mycobacterium bovis BCG yet their role during Mtb infection has remained unknown. Here, we examine the importance of a cluster of five GBPs on mouse chromosome 3 in controlling Mycobacterial infection. While M. bovis BCG is directly restricted by GBPs, we find that the GBPs on chromosome 3 do not contribute to the control of Mtb replication or the associated host response to infection. The differential effects of GBPs during Mtb versus M. bovis BCG infection is at least partially explained by the absence of the ESX1 secretion system from M. bovis BCG, since Mtb mutants lacking the ESX1 secretion system become similarly susceptible to GBP-mediated immune defense. Therefore, this specific genetic interaction between the murine host and Mycobacteria reveals a novel function for the ESX1 virulence system in the evasion of GBP-mediated immunity.

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