Importance of tumor necrosis factor-α (TNF-α) in the immune response to pulmonary cryptococcus neoformans (Cne) in mice

A. A. Izzo, K. Hoag, N. Street, M. F. Lipscomb

Research output: Contribution to journalArticle

Abstract

In a murine pulmonary Cne infection model, anti-TNF-α monoclonal antibodies (mAb), prevented resolution of the lung infection and the ability to adoptively transfer DTH from Cne infected to naive mice. Using this model we showed that resistant C.B-17 mice, capable of resolving a pulmonary Cne infection, mount a Th1 response as evidenced by increased IFN-γ and little IL-4 and IL-5 secretion by cultured lung and lung associated lymph node (LALN) cells. Susceptible C57BL/6 (B6) mice fail to efficiently clear a Cne lung infection and secrete significantly lower levels of IFN-γ and elevated levels of IL-5. We also found that alveolar macrophages (AM) from infected C.B-17 mice produced TNF-α when cultured in vitro, while AM from B6 mice did not. To investigate the role of TNF-α in the development of a Th1 response, C.B-17 mice were treated with anti-TNF-α mAb at days -1 and +1 of infection. Lung and LALN cells from these and control IgG treated mice were examined in vitro for cytokine production after Con A stimulation. Numbers and types of cells recruited to the lung during infection were examined. Cne-infected C.B-17 mice, when treated with anti-TNF-α mAb failed to resolve a pulmonary infection and produced a cytokine pattern in the lungs and LALN's that was indicative of a Th2 response (increased levels of IL-4 and IL-5). Furthermore, although both groups recruited equal numbers of cells into their lungs, the anti-TNF-α treated mice recruited increased numbers of eosinophils. These results clearly show that in C.B-17 mice TNF-α is important in initiating a Th1 response to pulmonary Cne infection.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

Fingerprint

Cryptococcus neoformans
tumor necrosis factors
Tumor Necrosis Factor-alpha
lungs
immune response
Lung
mice
Interleukin-5
Monoclonal Antibodies
Infection
infection
interleukin-5
Interleukin-4
Cytokines
monoclonal antibodies
Alveolar Macrophages
interleukin-4
lymph nodes
macrophages
cytokines

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Importance of tumor necrosis factor-α (TNF-α) in the immune response to pulmonary cryptococcus neoformans (Cne) in mice. / Izzo, A. A.; Hoag, K.; Street, N.; Lipscomb, M. F.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

@article{aad8109d24eb49dc8ae8c9513359c893,
title = "Importance of tumor necrosis factor-α (TNF-α) in the immune response to pulmonary cryptococcus neoformans (Cne) in mice",
abstract = "In a murine pulmonary Cne infection model, anti-TNF-α monoclonal antibodies (mAb), prevented resolution of the lung infection and the ability to adoptively transfer DTH from Cne infected to naive mice. Using this model we showed that resistant C.B-17 mice, capable of resolving a pulmonary Cne infection, mount a Th1 response as evidenced by increased IFN-γ and little IL-4 and IL-5 secretion by cultured lung and lung associated lymph node (LALN) cells. Susceptible C57BL/6 (B6) mice fail to efficiently clear a Cne lung infection and secrete significantly lower levels of IFN-γ and elevated levels of IL-5. We also found that alveolar macrophages (AM) from infected C.B-17 mice produced TNF-α when cultured in vitro, while AM from B6 mice did not. To investigate the role of TNF-α in the development of a Th1 response, C.B-17 mice were treated with anti-TNF-α mAb at days -1 and +1 of infection. Lung and LALN cells from these and control IgG treated mice were examined in vitro for cytokine production after Con A stimulation. Numbers and types of cells recruited to the lung during infection were examined. Cne-infected C.B-17 mice, when treated with anti-TNF-α mAb failed to resolve a pulmonary infection and produced a cytokine pattern in the lungs and LALN's that was indicative of a Th2 response (increased levels of IL-4 and IL-5). Furthermore, although both groups recruited equal numbers of cells into their lungs, the anti-TNF-α treated mice recruited increased numbers of eosinophils. These results clearly show that in C.B-17 mice TNF-α is important in initiating a Th1 response to pulmonary Cne infection.",
author = "Izzo, {A. A.} and K. Hoag and N. Street and Lipscomb, {M. F.}",
year = "1998",
month = "3",
day = "20",
language = "English (US)",
volume = "12",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "5",

}

TY - JOUR

T1 - Importance of tumor necrosis factor-α (TNF-α) in the immune response to pulmonary cryptococcus neoformans (Cne) in mice

AU - Izzo, A. A.

AU - Hoag, K.

AU - Street, N.

AU - Lipscomb, M. F.

PY - 1998/3/20

Y1 - 1998/3/20

N2 - In a murine pulmonary Cne infection model, anti-TNF-α monoclonal antibodies (mAb), prevented resolution of the lung infection and the ability to adoptively transfer DTH from Cne infected to naive mice. Using this model we showed that resistant C.B-17 mice, capable of resolving a pulmonary Cne infection, mount a Th1 response as evidenced by increased IFN-γ and little IL-4 and IL-5 secretion by cultured lung and lung associated lymph node (LALN) cells. Susceptible C57BL/6 (B6) mice fail to efficiently clear a Cne lung infection and secrete significantly lower levels of IFN-γ and elevated levels of IL-5. We also found that alveolar macrophages (AM) from infected C.B-17 mice produced TNF-α when cultured in vitro, while AM from B6 mice did not. To investigate the role of TNF-α in the development of a Th1 response, C.B-17 mice were treated with anti-TNF-α mAb at days -1 and +1 of infection. Lung and LALN cells from these and control IgG treated mice were examined in vitro for cytokine production after Con A stimulation. Numbers and types of cells recruited to the lung during infection were examined. Cne-infected C.B-17 mice, when treated with anti-TNF-α mAb failed to resolve a pulmonary infection and produced a cytokine pattern in the lungs and LALN's that was indicative of a Th2 response (increased levels of IL-4 and IL-5). Furthermore, although both groups recruited equal numbers of cells into their lungs, the anti-TNF-α treated mice recruited increased numbers of eosinophils. These results clearly show that in C.B-17 mice TNF-α is important in initiating a Th1 response to pulmonary Cne infection.

AB - In a murine pulmonary Cne infection model, anti-TNF-α monoclonal antibodies (mAb), prevented resolution of the lung infection and the ability to adoptively transfer DTH from Cne infected to naive mice. Using this model we showed that resistant C.B-17 mice, capable of resolving a pulmonary Cne infection, mount a Th1 response as evidenced by increased IFN-γ and little IL-4 and IL-5 secretion by cultured lung and lung associated lymph node (LALN) cells. Susceptible C57BL/6 (B6) mice fail to efficiently clear a Cne lung infection and secrete significantly lower levels of IFN-γ and elevated levels of IL-5. We also found that alveolar macrophages (AM) from infected C.B-17 mice produced TNF-α when cultured in vitro, while AM from B6 mice did not. To investigate the role of TNF-α in the development of a Th1 response, C.B-17 mice were treated with anti-TNF-α mAb at days -1 and +1 of infection. Lung and LALN cells from these and control IgG treated mice were examined in vitro for cytokine production after Con A stimulation. Numbers and types of cells recruited to the lung during infection were examined. Cne-infected C.B-17 mice, when treated with anti-TNF-α mAb failed to resolve a pulmonary infection and produced a cytokine pattern in the lungs and LALN's that was indicative of a Th2 response (increased levels of IL-4 and IL-5). Furthermore, although both groups recruited equal numbers of cells into their lungs, the anti-TNF-α treated mice recruited increased numbers of eosinophils. These results clearly show that in C.B-17 mice TNF-α is important in initiating a Th1 response to pulmonary Cne infection.

UR - http://www.scopus.com/inward/record.url?scp=33749345421&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749345421&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33749345421

VL - 12

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 5

ER -