Adipose tissue regulates pulmonary pathology during TB infection

Janeesh Plakkal Ayyappan, Usha Ganapathi, Kezia Lizardo, Christopher Vinnard, Selvakumar Subbian, David Perlin, Jyothi F. Nagajyothi

Research output: Contribution to journalArticle

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, remains a major cause of mortality and morbidity worldwide. One-third of the world population is infected with M. tuberculosis, and about 15 million people with latent tuberculosis infection (LTBI) reside in the United States. An estimated 10% of individuals with LTBI are at risk of progressing to active disease. Loss of body mass, or wasting, accompanied by a significant reduction of body fat is often associated with active TB disease and is considered to be immunosuppressive and a major determinant of severity and outcome of disease. While the lungs are the primary site of M. tuberculosis infection and TB manifestation, recent reports have shown that adipose tissue serves as an important reservoir for M. tuberculosis. In this article, we investigated the association between M. tuberculosis infection, adipose tissue, and TB disease progression using a transgenic inducible “fatless” model system, the FAT-ATTAC (fat apoptosis through targeted activation of caspase 8) mouse. By selectively ablating fat tissue during M. tuberculosis infection, we directly tested the role of fat cell loss and adipose tissue physiology in regulating pulmonary pathology, bacterial burden, and immune status. Our results confirm the presence of M. tuberculosis in fat tissue after aerosol infection of mice and show that loss of fat cells is associated with an increase in pulmonary M. tuberculosis burden and pathology. We conclude that acute loss of adipose tissue during LTBI may predispose the host to active TB disease. IMPORTANCE Although the lungs are the port of entry and the predominant site of TB disease manifestation, we and others have demonstrated that M. tuberculosis also persists in adipose tissue of aerosol-infected animals and directly or indirectly alters adipose tissue physiology, which in turn alters whole-body immuno-metabolic homeostasis. Our present report demonstrates a direct effect of loss of adipocytes (fat cells) on promoting the severity of pulmonary pathogenesis during TB, advancing our understanding of the pathogenic interactions between wasting and TB activation/ reactivation.

Original languageEnglish (US)
Article numbere02771-18
JournalmBio
Volume10
Issue number2
DOIs
StatePublished - Mar 1 2019

Fingerprint

Mycobacterium tuberculosis
Adipose Tissue
Tuberculosis
Pathology
Lung
Mycobacterium Infections
Infection
Latent Tuberculosis
Adipocytes
Fats
Aerosols
Caspase 8
Mycobacterium
Immunosuppressive Agents
Pulmonary Tuberculosis
Disease Progression
Homeostasis
Apoptosis
Morbidity
Mortality

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Virology

Keywords

  • Adipose tissue
  • Fat loss
  • Foamy macrophages
  • Mycobacterium tuberculosis
  • Tb reactivation
  • Wasting

Cite this

@article{3001038085194a4ba5baea82c63c0b62,
title = "Adipose tissue regulates pulmonary pathology during TB infection",
abstract = "Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, remains a major cause of mortality and morbidity worldwide. One-third of the world population is infected with M. tuberculosis, and about 15 million people with latent tuberculosis infection (LTBI) reside in the United States. An estimated 10{\%} of individuals with LTBI are at risk of progressing to active disease. Loss of body mass, or wasting, accompanied by a significant reduction of body fat is often associated with active TB disease and is considered to be immunosuppressive and a major determinant of severity and outcome of disease. While the lungs are the primary site of M. tuberculosis infection and TB manifestation, recent reports have shown that adipose tissue serves as an important reservoir for M. tuberculosis. In this article, we investigated the association between M. tuberculosis infection, adipose tissue, and TB disease progression using a transgenic inducible “fatless” model system, the FAT-ATTAC (fat apoptosis through targeted activation of caspase 8) mouse. By selectively ablating fat tissue during M. tuberculosis infection, we directly tested the role of fat cell loss and adipose tissue physiology in regulating pulmonary pathology, bacterial burden, and immune status. Our results confirm the presence of M. tuberculosis in fat tissue after aerosol infection of mice and show that loss of fat cells is associated with an increase in pulmonary M. tuberculosis burden and pathology. We conclude that acute loss of adipose tissue during LTBI may predispose the host to active TB disease. IMPORTANCE Although the lungs are the port of entry and the predominant site of TB disease manifestation, we and others have demonstrated that M. tuberculosis also persists in adipose tissue of aerosol-infected animals and directly or indirectly alters adipose tissue physiology, which in turn alters whole-body immuno-metabolic homeostasis. Our present report demonstrates a direct effect of loss of adipocytes (fat cells) on promoting the severity of pulmonary pathogenesis during TB, advancing our understanding of the pathogenic interactions between wasting and TB activation/ reactivation.",
keywords = "Adipose tissue, Fat loss, Foamy macrophages, Mycobacterium tuberculosis, Tb reactivation, Wasting",
author = "Ayyappan, {Janeesh Plakkal} and Usha Ganapathi and Kezia Lizardo and Christopher Vinnard and Selvakumar Subbian and David Perlin and Nagajyothi, {Jyothi F.}",
year = "2019",
month = "3",
day = "1",
doi = "10.1128/mBio.02771-18",
language = "English (US)",
volume = "10",
journal = "mBio",
issn = "2161-2129",
publisher = "American Society for Microbiology",
number = "2",

}

Adipose tissue regulates pulmonary pathology during TB infection. / Ayyappan, Janeesh Plakkal; Ganapathi, Usha; Lizardo, Kezia; Vinnard, Christopher; Subbian, Selvakumar; Perlin, David; Nagajyothi, Jyothi F.

In: mBio, Vol. 10, No. 2, e02771-18, 01.03.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Adipose tissue regulates pulmonary pathology during TB infection

AU - Ayyappan, Janeesh Plakkal

AU - Ganapathi, Usha

AU - Lizardo, Kezia

AU - Vinnard, Christopher

AU - Subbian, Selvakumar

AU - Perlin, David

AU - Nagajyothi, Jyothi F.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, remains a major cause of mortality and morbidity worldwide. One-third of the world population is infected with M. tuberculosis, and about 15 million people with latent tuberculosis infection (LTBI) reside in the United States. An estimated 10% of individuals with LTBI are at risk of progressing to active disease. Loss of body mass, or wasting, accompanied by a significant reduction of body fat is often associated with active TB disease and is considered to be immunosuppressive and a major determinant of severity and outcome of disease. While the lungs are the primary site of M. tuberculosis infection and TB manifestation, recent reports have shown that adipose tissue serves as an important reservoir for M. tuberculosis. In this article, we investigated the association between M. tuberculosis infection, adipose tissue, and TB disease progression using a transgenic inducible “fatless” model system, the FAT-ATTAC (fat apoptosis through targeted activation of caspase 8) mouse. By selectively ablating fat tissue during M. tuberculosis infection, we directly tested the role of fat cell loss and adipose tissue physiology in regulating pulmonary pathology, bacterial burden, and immune status. Our results confirm the presence of M. tuberculosis in fat tissue after aerosol infection of mice and show that loss of fat cells is associated with an increase in pulmonary M. tuberculosis burden and pathology. We conclude that acute loss of adipose tissue during LTBI may predispose the host to active TB disease. IMPORTANCE Although the lungs are the port of entry and the predominant site of TB disease manifestation, we and others have demonstrated that M. tuberculosis also persists in adipose tissue of aerosol-infected animals and directly or indirectly alters adipose tissue physiology, which in turn alters whole-body immuno-metabolic homeostasis. Our present report demonstrates a direct effect of loss of adipocytes (fat cells) on promoting the severity of pulmonary pathogenesis during TB, advancing our understanding of the pathogenic interactions between wasting and TB activation/ reactivation.

AB - Tuberculosis (TB), caused by Mycobacterium tuberculosis infection, remains a major cause of mortality and morbidity worldwide. One-third of the world population is infected with M. tuberculosis, and about 15 million people with latent tuberculosis infection (LTBI) reside in the United States. An estimated 10% of individuals with LTBI are at risk of progressing to active disease. Loss of body mass, or wasting, accompanied by a significant reduction of body fat is often associated with active TB disease and is considered to be immunosuppressive and a major determinant of severity and outcome of disease. While the lungs are the primary site of M. tuberculosis infection and TB manifestation, recent reports have shown that adipose tissue serves as an important reservoir for M. tuberculosis. In this article, we investigated the association between M. tuberculosis infection, adipose tissue, and TB disease progression using a transgenic inducible “fatless” model system, the FAT-ATTAC (fat apoptosis through targeted activation of caspase 8) mouse. By selectively ablating fat tissue during M. tuberculosis infection, we directly tested the role of fat cell loss and adipose tissue physiology in regulating pulmonary pathology, bacterial burden, and immune status. Our results confirm the presence of M. tuberculosis in fat tissue after aerosol infection of mice and show that loss of fat cells is associated with an increase in pulmonary M. tuberculosis burden and pathology. We conclude that acute loss of adipose tissue during LTBI may predispose the host to active TB disease. IMPORTANCE Although the lungs are the port of entry and the predominant site of TB disease manifestation, we and others have demonstrated that M. tuberculosis also persists in adipose tissue of aerosol-infected animals and directly or indirectly alters adipose tissue physiology, which in turn alters whole-body immuno-metabolic homeostasis. Our present report demonstrates a direct effect of loss of adipocytes (fat cells) on promoting the severity of pulmonary pathogenesis during TB, advancing our understanding of the pathogenic interactions between wasting and TB activation/ reactivation.

KW - Adipose tissue

KW - Fat loss

KW - Foamy macrophages

KW - Mycobacterium tuberculosis

KW - Tb reactivation

KW - Wasting

UR - http://www.scopus.com/inward/record.url?scp=85064994936&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064994936&partnerID=8YFLogxK

U2 - 10.1128/mBio.02771-18

DO - 10.1128/mBio.02771-18

M3 - Article

C2 - 30992360

AN - SCOPUS:85064994936

VL - 10

JO - mBio

JF - mBio

SN - 2161-2129

IS - 2

M1 - e02771-18

ER -