Mycobacterium tuberculosis growth control by lung macrophages and CD8 cells from patient contacts

Claudia Carranza, Esmeralda Juárez, Martha Torres, Jerrold J. Ellner, Eduardo Sada, Stephan K. Schwander

Research output: Contribution to journalArticle

Abstract

Rationale: Healthy household contacts (HHCs) of patients with active pulmonary tuberculosis are exposed aerogenically to Mycobacterium tuberculosis (Mtb), thus permitting the study of protective local immunity. Objectives: To assess alveolar macrophage (AM) and autologous blood CD4 and CD8 T-cell-mediated Mtb growth control in HHCs and healthy, unexposed community control subjects (CCs). Methods: AMs were infected with Mtb strains H37Ra and H 37Rv at multiplicities of infection 0.1 and 1. Mtb colony-forming units were evaluated on Days 1, 4, and 7. Main Results: CD8 T cells from HHCs in 1:1 cocultures with AMs significantly (p <0.05) increased Mtb growth control by AMs. In CCs, no detectable contribution of CD8 T cells to Mtb growth control was observed. CD4 T cells did not increase Mtb growth control in HHCs or in CCs. IFN-γ, nitric oxide, and tumor necrosis factor were determined as potential mediators of Mtb growth control in AMs and AM/CD8 and AM/CD4 cocultures. IFN-γ production in AM/CD4 was twofold higher than that in AM/CD8 cocultures in both HHCs and CCs (p <0.05). Nitric oxide production from AMs of HHCs increased on Days 4 and 7 and was undetectable in AMs from CCs. IFN-γ and nitric acid concentrations and Mtb growth control were not correlated. Tumor necrosis factor levels were significantly increased in AM/CD8 cocultures from HHCs compared with AM/CD8 cocultures from CCs (p <0.05). Conclusion: Aerogenic exposure to Mtb in HHCs leads to expansion of Mtb-specific effector CD8 T cells that limit Mtb growth in autologous AMs.

Original languageEnglish (US)
Pages (from-to)238-245
Number of pages8
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume173
Issue number2
DOIs
StatePublished - Jan 15 2006
Externally publishedYes

Fingerprint

Mycobacterium tuberculosis
Macrophages
Alveolar Macrophages
Lung
Growth
Coculture Techniques
T-Lymphocytes
Nitric Oxide
Tumor Necrosis Factor-alpha
Nitric Acid
Pulmonary Tuberculosis
Immunity
Stem Cells

Keywords

  • Interferon type II
  • Macrophages, alveolar
  • Mycobacterium tuberculosis
  • Nitric oxide
  • T lymphocytes, effector

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Mycobacterium tuberculosis growth control by lung macrophages and CD8 cells from patient contacts. / Carranza, Claudia; Juárez, Esmeralda; Torres, Martha; Ellner, Jerrold J.; Sada, Eduardo; Schwander, Stephan K.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 173, No. 2, 15.01.2006, p. 238-245.

Research output: Contribution to journalArticle

Carranza, Claudia ; Juárez, Esmeralda ; Torres, Martha ; Ellner, Jerrold J. ; Sada, Eduardo ; Schwander, Stephan K. / Mycobacterium tuberculosis growth control by lung macrophages and CD8 cells from patient contacts. In: American Journal of Respiratory and Critical Care Medicine. 2006 ; Vol. 173, No. 2. pp. 238-245.
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abstract = "Rationale: Healthy household contacts (HHCs) of patients with active pulmonary tuberculosis are exposed aerogenically to Mycobacterium tuberculosis (Mtb), thus permitting the study of protective local immunity. Objectives: To assess alveolar macrophage (AM) and autologous blood CD4 and CD8 T-cell-mediated Mtb growth control in HHCs and healthy, unexposed community control subjects (CCs). Methods: AMs were infected with Mtb strains H37Ra and H 37Rv at multiplicities of infection 0.1 and 1. Mtb colony-forming units were evaluated on Days 1, 4, and 7. Main Results: CD8 T cells from HHCs in 1:1 cocultures with AMs significantly (p <0.05) increased Mtb growth control by AMs. In CCs, no detectable contribution of CD8 T cells to Mtb growth control was observed. CD4 T cells did not increase Mtb growth control in HHCs or in CCs. IFN-γ, nitric oxide, and tumor necrosis factor were determined as potential mediators of Mtb growth control in AMs and AM/CD8 and AM/CD4 cocultures. IFN-γ production in AM/CD4 was twofold higher than that in AM/CD8 cocultures in both HHCs and CCs (p <0.05). Nitric oxide production from AMs of HHCs increased on Days 4 and 7 and was undetectable in AMs from CCs. IFN-γ and nitric acid concentrations and Mtb growth control were not correlated. Tumor necrosis factor levels were significantly increased in AM/CD8 cocultures from HHCs compared with AM/CD8 cocultures from CCs (p <0.05). Conclusion: Aerogenic exposure to Mtb in HHCs leads to expansion of Mtb-specific effector CD8 T cells that limit Mtb growth in autologous AMs.",
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T1 - Mycobacterium tuberculosis growth control by lung macrophages and CD8 cells from patient contacts

AU - Carranza, Claudia

AU - Juárez, Esmeralda

AU - Torres, Martha

AU - Ellner, Jerrold J.

AU - Sada, Eduardo

AU - Schwander, Stephan K.

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N2 - Rationale: Healthy household contacts (HHCs) of patients with active pulmonary tuberculosis are exposed aerogenically to Mycobacterium tuberculosis (Mtb), thus permitting the study of protective local immunity. Objectives: To assess alveolar macrophage (AM) and autologous blood CD4 and CD8 T-cell-mediated Mtb growth control in HHCs and healthy, unexposed community control subjects (CCs). Methods: AMs were infected with Mtb strains H37Ra and H 37Rv at multiplicities of infection 0.1 and 1. Mtb colony-forming units were evaluated on Days 1, 4, and 7. Main Results: CD8 T cells from HHCs in 1:1 cocultures with AMs significantly (p <0.05) increased Mtb growth control by AMs. In CCs, no detectable contribution of CD8 T cells to Mtb growth control was observed. CD4 T cells did not increase Mtb growth control in HHCs or in CCs. IFN-γ, nitric oxide, and tumor necrosis factor were determined as potential mediators of Mtb growth control in AMs and AM/CD8 and AM/CD4 cocultures. IFN-γ production in AM/CD4 was twofold higher than that in AM/CD8 cocultures in both HHCs and CCs (p <0.05). Nitric oxide production from AMs of HHCs increased on Days 4 and 7 and was undetectable in AMs from CCs. IFN-γ and nitric acid concentrations and Mtb growth control were not correlated. Tumor necrosis factor levels were significantly increased in AM/CD8 cocultures from HHCs compared with AM/CD8 cocultures from CCs (p <0.05). Conclusion: Aerogenic exposure to Mtb in HHCs leads to expansion of Mtb-specific effector CD8 T cells that limit Mtb growth in autologous AMs.

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KW - Interferon type II

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KW - Nitric oxide

KW - T lymphocytes, effector

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