Type VII secretion — mycobacteria show the way

Abdallah, Abdallah; Pittius, Nicolaas C. Gey van; Champion, Patricia A.; Cox, Jeffery S.; Luirink, Joen; Vandenbroucke-Grauls, Christina M. J. E.; Appelmelk, Ben J.; Bitter, Wilbert

doi:10.1038/nrmicro1773

Cited by 632 publications

(651 citation statements)

References 79 publications

Supporting

Mentioning

635

Contrasting

Unclassified

Order By: Relevance

“…The ESX‐1 type VII secretion system (T7SS) that is lacking from most of the non‐pathogenic mycobacterial strains (Abdallah et al ., 2007) is required for Mtb localization in the cytosol. As part of the T7SS, ESAT‐6 protein is believed to make pores on cellular membranes (Hsu et al ., 2003; Jonge et al ., 2007; Wong and Jacobs, 2011).…”

Section: Cell Autonomous Defence Mechanisms In Tbmentioning

confidence: 99%

The innate immune response in human tuberculosis

2015

View full text Add to dashboard Cite

Summary M ycobacterium tuberculosis (Mtb) infection can be cleared by the innate immune system before the initiation of an adaptive immune response. This innate protection requires a variety of robust cell autonomous responses from many different host immune cell types. However, Mtb has evolved strategies to circumvent some of these defences. In this mini‐review, we discuss these host–pathogen interactions with a focus on studies performed in human cells and/or supported by human genetics studies (such as genome‐wide association studies).

show abstract

Section: Cell Autonomous Defence Mechanisms In Tbmentioning

confidence: 99%

The innate immune response in human tuberculosis

2015

View full text Add to dashboard Cite

show abstract

“…Then cells were fixed and permeabilized according to the manufacturer's instructions (Perm2, BD Biosciences) before FITC-anti-IL-6, FITC-anti-IL-10 (BD Biosciences), PE-anti-IL-1ß, FITC-anti-TNF-α, PE-anti-IL12 (eBioscience), or the corresponding isotypes were added. Data acquisition (≈5 × 10 5 events) was carried out using a FACScalibur flow cytometer equipped with CellQuest software [58]. DC or Mo populations were gated according to its forward and side scatter proprieties.…”

Section: Immunofluorescence Analysismentioning

confidence: 99%

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

et al. 2013

View full text Add to dashboard Cite

Tuberculosis (TB) is one of the world's most pernicious diseases mainly due to immune evasion strategies displayed by its causative agent Mycobacterium tuberculosis (Mtb). Blood monocytes (Mos) represent an important source of DCs during chronic infections; consequently, the alteration of their differentiation constitutes an escape mechanism leading to mycobacterial persistence. We evaluated whether the CD16 + /CD16 − Mo ratio could be associated with the impaired Mo differentiation into DCs found in TB patients. The phenotype and ability to stimulate Mtb-specific memory clones DCs from isolated Mo subsets were assessed. We found that CD16 − Mos differentiated into CD1a + DC-SIGN high cells achieving an efficient recall response, while CD16 + Mos differentiated into a CD1a − DC-SIGN low population characterized by a poor mycobacterial Ag-presenting capacity. The high and sustained phosphorylated p38 expression observed in CD16 + Mos was involved in the altered DC profile given that its blockage restored DC phenotype and its activation impaired CD16 − Mo differentiation. Furthermore, depletion of CD16 + Mos indeed improved the differentiation of Mos from TB patients toward CD1a + DC-SIGN high DCs. Therefore, Mos from TB patients are less prone to differentiate into DCs due to their increased proportion of CD16 + Mos, suggesting that during Mtb infection Mo subsets may have different fates after entering the lungs. Keywords: Dendritic cells r Monocyte differentiation r Tuberculosis See accompanying Commentary by Lugo-Villarino and NeyrollesAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionMonocytes (Mos) are large circulating leukocytes of the myeloid lineage that mediate essential functions of innate immunity including phagocytosis and cytokine production [1,2]. Mos are produced Correspondence: Dr. Luciana Balboa e-mail: luciana_balboa@hotmail.com in the bone marrow and released into the blood, and circulate in blood or reside in a spleen reservoir and, upon tissue infiltration they can differentiate into macrophages (M s) or DCs. Although human blood Mos are a highly heterogeneous population, two main subsets have been described: CD14 + CD16 − "classical" Mos are the major Mo population and CD14 + CD16 + Mos, the minor one (5-10% of total Mos). The latter subset has a more mature phenotype and an enhanced proinflammatory activity [3]. This heterogeneity has led to the hypothesis that Mos are committed to specific functions prior to tissue infiltration [4]. Also, C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 336Luciana Balboa et al. Eur. J. Immunol. 2013. 43: 335-347 an imbalance in the relative proportions of the subsets during acute inflammation [5] and several infectious diseases [6][7][8][9][10] including tuberculosis (TB) [11,12] has been described. TB, a disease that mainly affects the respiratory system, infects onethird of the world's population and kills 2 million people each year [13]. The success o...

show abstract

“…1). Specifically, it is present at 52-166 amino acids in MAP_1272c, followed by a glutamine-rich region (169-273) containing the repeat sequence (QQAPLQ) 6 .…”

Section: Characteristics Of Map_1204 and Map_1272cmentioning

confidence: 99%

“…[3][4][5] This economically significant veterinary pathogen is among the Mycobacteria which all contain a unique cell wall structure that includes mycolic acids covering the lipoarabinogalactan layer with a foundational lattice of muropeptide cross-linked peptidoglycan. 6 Implicit with this sturdy cell wall are hydrolytic mechanisms required for cell division, peptidoglycan remodeling, nutrient uptake, as well as other biological processes. Thus the peptidoglycan layer in particular must be constantly modified during growth and at least partially disassembled to separate daughter cells during the final stages of cell division.…”

Section: Introductionmentioning

confidence: 99%

NlpC/P60 domain‐containing proteins of Mycobacterium avium subspecies paratuberculosis that differentially bind and hydrolyze peptidoglycan

et al. 2016

View full text Add to dashboard Cite

A subset of proteins containing NlpC/P60 domains are bacterial peptidoglycan hydrolases that cleave noncanonical peptide linkages and contribute to cell wall remodeling as well as cell separation during late stages of division. Some of these proteins have been shown to cleave peptidoglycan in Mycobacterium tuberculosis and play a role in Mycobacterium marinum virulence of zebra fish; however, there are still significant knowledge gaps concerning the molecular function of these proteins in Mycobacterium avium subspecies paratuberculosis (MAP). The MAP genome sequence encodes five NlpC/P60 domain-containing proteins. We describe atomic resolution crystal structures of two such MAP proteins, MAP_1272c and MAP_1204. These crystal structures, combined with functional assays to measure peptidoglycan cleavage activity, led to the observation that MAP_1272c does not have a functional catalytic core for peptidoglycan hydrolysis. Furthermore, the structure and sequence of MAP_1272c demonstrate that the catalytic residues normally required for hydrolysis are absent, and the protein does not bind peptidoglycan as efficiently as MAP_1204. While the NlpC/P60 catalytic triad is present in MAP_1204, changing the catalytic cysteine-155 residue to a serine significantly diminished catalytic activity, but did not affect binding to peptidoglycan. Collectively, these findings suggest a broader functional repertoire for NlpC/P60 domain-containing proteins than simply hydrolases. Keywords: Mycobacterium; Johne's disease; crystal structure; peptidoglycan; proteins; antigens; paratuberculosis Additional Supporting Information may be found in the online version of this article.Importance: Johne's disease in ruminant livestock is caused by the bacterium Mycobacterium avium subspecies paratuberculosis. This research describes the functional aspects of two proteins that show promise in a subunit vaccine for Johne's disease. Through crystal structure determination and amino acid modification, we demonstrate that although both proteins have a similar structure, one of them lacked hydrolytic activity on peptidoglycan. We show that a specific amino acid is likely responsible for this lack of hydrolytic activity.

show abstract

Type VII secretion — mycobacteria show the way

Cited by 632 publications

References 79 publications

The innate immune response in human tuberculosis

The innate immune response in human tuberculosis

Impaired dendritic cell differentiation of CD16‐positive monocytes in tuberculosis: Role of p38 MAPK

NlpC/P60 domain‐containing proteins of Mycobacterium avium subspecies paratuberculosis that differentially bind and hydrolyze peptidoglycan

Contact Info

Product

Resources

About