Effects of protein calorie malnutrition on tuberculosis in mice

John Chan, Yu Tian, Kathryn E. Tanakat, Ming S. Tsang, Keming Yu, Padmini Salgame, Dinah Carroll, Yvonne Kress, Rachel Teitelbaum, Barry R. Bloom

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

Infectious diseases and malnutrition represent major burdens afflicting millions of people in developing countries. Both conditions affect individuals in industrialized nations, particularly the aged, the HIV- infected, and people with chronic diseases. While malnutrition is known to induce a state of immunodeficiency, the mechanisms responsible for compromised antimicrobial resistance in malnourished hosts remain obscure. In the present study, mice fed a 2% protein diet and developing protein calorie malnutrition, in contrast to well-nourished controls receiving a 20% protein diet, rapidly succumbed to infection with Mycobacterium tuberculosis. Malnourished mice exhibited a tissue-specific diminution in the expression of interferon γ, tumor necrosis factor α, and the inducible form of nitric oxide synthase in the lungs, but not the liver. The expression of these molecules critical to the production of mycobactericidal nitrogen oxides was depressed in malnourished animals in the lungs specifically at early times (<14 days) after infection. At later times, levels of expression became comparable to those in well-nourished controls, although the bacillary burden in the malnourished animals continued to rise. Nevertheless, urinary and serum nitrate contents, an index of total nitric oxide (NO) production in vivo, were not detectably diminished in malnourished, mycobacteria-infected mice. In contrast to the selective and early reduction of lymphokines and the inducible form of nitric oxide synthase in the lung, a marked diminution of the granulomatous reaction was observed in malnourished mice throughout the entire course of infection in all tissues examined (lungs, liver, and spleen). Remarkably, the progressively fatal course of tuberculosis observed in the malnourished mice could be reversed by restoring a full protein (20%) diet. The results indicate that protein calorie malnutrition selectively compromises several components of the cellular immune response that are important for containing and restricting tuberculous infection, and suggest that malnutrition-induced susceptibility to some infectious diseases can be reversed or ameliorated by nutritional intervention.

Original languageEnglish (US)
Pages (from-to)14857-14861
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number25
DOIs
StatePublished - Dec 10 1996

Keywords

  • granuloma
  • interferon γ
  • nitric oxide synthase
  • reactive nitrogen intermediates
  • tumor necrosis factor α

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Effects of protein calorie malnutrition on tuberculosis in mice'. Together they form a unique fingerprint.

Cite this