NDLI: Mycobacterium tuberculosis impairs dendritic cell functions through the serine hydrolase Hip1

Content Provider	PubMed Central
Author	Madan-lala, Ranjna Sia, Jonathan Kevin King, Rebecca Adekambi, Toidi Monin, Leticia Khader, Shabaana A. Pulendran, Bali Rengarajan, Jyothi
Abstract	Mycobacterium tuberculosis (Mtb) is a highly successful human pathogen that primarily resides in host phagocytes, such as macrophages and dendritic cells (DCs), and interferes with their functions. While multiple strategies used by Mtb to modulate macrophage responses have been discovered, interactions between Mtb and DCs are less well understood. DCs are the primary antigen presenting acells (APCs) of the immune system and play a central role in linking innate and adaptive immune responses to microbial pathogens. In this study we show that Mtb impairs DC cytokine secretion, maturation and antigen presentation through the cell envelope-associated serine hydrolase Hip1. Compared to wild type, a hip1 mutant strain of Mtb induced enhanced levels of the key T helper 1 (Th1)-inducing cytokine IL-12, as well as other proinflammatory cytokines (IL-23, IL-6, TNF-α, IL-1β, IL-18) in DCs via MyD88- and TLR2/9-dependent pathways, indicating that Hip1 restricts optimal DC inflammatory responses. Infection with the hip1 mutant also induced higher levels of MHC class II and co-stimulatory molecules, CD40 and CD86, indicating that Mtb impairs DC maturation through Hip1. Further, we show that Mtb promotes sub-optimal antigen presentation, as DCs infected with the hip1 mutant showed increased capacity to present antigen to OT-II- and early secreted antigenic target 6 (ESAT-6)-specific transgenic CD4 T cells and enhanced Th1 and Th17 polarization. Overall, these data show that Mtb impairs DC functions and modulates the nature of antigen-specific T cell responses, with important implications for vaccination strategies.
Related Links	http://dx.doi.org/10.4049/jimmunol.1303185
Ending Page	4272
Page Count	10
Starting Page	4263
File Format	PDF
ISSN	00221767
e-ISSN	15506606
Journal	Journal of immunology (Baltimore, Md. : 1950)
Issue Number	9
Volume Number	192
Language	English
Publisher Date	2014-05-01
Access Restriction	Open
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Mycobacterium tuberculosis impairs dendritic cell functions through the serine hydrolase Hip1.

Mycobacterium tuberculosis heat-shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin-10 production and inhibits T-cell proliferation in vitro

Enhancement of Tumor-Specific T Cell–Mediated Immunity in Dendritic Cell–Based Vaccines by Mycobacterium tuberculosis Heat Shock Protein X

Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone

Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection

Characterization of Dendritic Cell and Regulatory T Cell Functions against Mycobacterium tuberculosis Infection

DC-SIGN Is the Major Mycobacterium tuberculosis Receptor on Human Dendritic Cells

HIV-1 gp120 impairs the induction of B cell responses by TLR9-activated plasmacytoid dendritic cells

Mycobacterium tuberculosis Hip1 Modulates Macrophage Responses through Proteolysis of GroEL2

Mycobacterium tuberculosis impairs dendritic cell functions through the serine hydrolase Hip1

Similar Documents

Mycobacterium tuberculosis impairs dendritic cell functions through the serine hydrolase Hip1.

Mycobacterium tuberculosis heat-shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin-10 production and inhibits T-cell proliferation in vitro

Enhancement of Tumor-Specific T Cell–Mediated Immunity in Dendritic Cell–Based Vaccines by Mycobacterium tuberculosis Heat Shock Protein X

Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone

Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection

Characterization of Dendritic Cell and Regulatory T Cell Functions against Mycobacterium tuberculosis Infection

DC-SIGN Is the Major Mycobacterium tuberculosis Receptor on Human Dendritic Cells

HIV-1 gp120 impairs the induction of B cell responses by TLR9-activated plasmacytoid dendritic cells

Mycobacterium tuberculosis Hip1 Modulates Macrophage Responses through Proteolysis of GroEL2

Mycobacterium tuberculosis impairs dendritic cell functions through the serine hydrolase Hip1