Intranasal Immunization with DnaK Protein Induces Protective Mucosal Immunity against Tuberculosis in CD4-Depleted Mice

Frontiers in Cellular and Infection Microbiology
Yu-Min ChuangChien-Fu Hung

Abstract

Mycobacterium tuberculosis (Mtb) remains a global health challenge due to the limited efficacy of the Mtb vaccine in current use, Bacillus Calmette-Guérin (BCG). To date, there is no available vaccine for immunocompromised individuals. Thus, there is an urgent need to develop a new vaccine candidate which can induce mucosal immunity in hosts with different immune statuses. DnaK (HSP70) has been shown to induce protective immunity against Mtb infection when administered by DNA vaccine; however, the protection is inferior to that induced by the BCG vaccine. In our study, we vaccinated C57BL/6J mice with DnaK protein alone. Subcutaneous or intranasal vaccination with DnaK generated IFNγ-secreting CD4+ T cells in the spleen, but only intranasal vaccination generated IL-17-releasing CD4+ T cells in the lungs, even when circulating CD4+ T cells were diminished. Furthermore, intranasal vaccination with DnaK generated tissue resident CD4+ T cells in the lungs. Vaccination with DnaK alone resulted in protective immunity comparable to BCG vaccination against tuberculosis in mice. Our results demonstrate that intranasal vaccination with DnaK can generate mucosal immunity in immunocompromised or immunocompetent mice and DnaK vaccination ca...Continue Reading

References

Apr 1, 1996·Annals of Internal Medicine·A S FauciD Weissman
Aug 1, 1996·Nature Medicine·R E TasconD B Lowrie
Jun 1, 1997·Vaccine·D B LowrieR E Tascon
Jan 22, 2003·Immunology and Cell Biology·Warwick J Britton, Umaimainthan Palendira
Mar 27, 2003·Molecular Microbiology·Christopher M SassettiEric J Rubin
Jul 14, 2005·Nature Reviews. Microbiology·Peter Andersen, T Mark Doherty
Oct 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Khalid SendideZakaria Hmama
Jun 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marsha S RussellSubash Sad
Sep 4, 2007·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Mamta KalraG K Khuller
Oct 7, 2008·Vaccine·Amit LahiriDipshikha Chakravortty
Jan 2, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Cornelia L TrimbleT C Wu
Mar 12, 2009·Journal of Leukocyte Biology·Min-Fu Tsan, Baochong Gao
Sep 30, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·You-Sun KimYoon-Keun Kim
Apr 8, 2010·Critical Reviews in Immunology·Anna U BielinskaJames R Baker
Aug 18, 2010·Vaccine·Folkert SteinhagenDennis M Klinman
Jun 12, 2013·Annual Review of Biochemistry·Yujin E KimF Ulrich Hartl
Nov 7, 2013·Journal of Innate Immunity·Johanneke KleinnijenhuisMihai G Netea
Apr 1, 2014·The Journal of Allergy and Clinical Immunology·Beatriz E MarcianoSergio D Rosenzweig
Jul 25, 2014·PLoS Genetics·Allison Fay, Michael S Glickman
Dec 17, 2014·The Journal of Infectious Diseases·Hiroyuki SaigaStefan H E Kaufmann
Apr 14, 2016·Nature Communications·Helen A FletcherHelen McShane
Jun 23, 2016·Mucosal Immunology·S M CaucheteuxW E Paul
Jul 2, 2016·Science·David BalchinF Ulrich Hartl

❮ Previous
Next ❯

Methods Mentioned

BETA
genetic modification
protein folding
flow cytometry
ELISA
lavage

Software Mentioned

FlowJo
MedCalc

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.