A genetic model of stress displays decreased lymphocytes and impaired antibody responses without altered susceptibility to Streptococcus pneumoniae

Susan Murray, H. R. Lallman, A. D. Heard, Marvin Rittenberg, Mary Stenzel-Poore

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Stress pathways affect immune function, the most notable of these pathways being activation of the hypothalamic-pituitary-adrenal (HPA) axis. Although HPA activation has generally been relegated to an immunosuppressive role, recent evidence suggests that stress and HPA activation can be immunoenhancing in certain situations. To investigate specific effects of stress on immune function, we used a genetic model of chronic stress wherein transgenic mice overexpress corticotropin-releasing hormone (CRH), a primary mediator of the stress response. In these mice, CRH is overproduced in the brain, leading to chronic activation of the HPA axis. We found that CRH-transgenic mice have decreased leukocyte numbers in lymphoid compartments, with preferential loss of B lymphocytes. They also exhibit decreased Ab production and impaired isotype switching in response to immunization with a thymus-dependent Ag, phosphocholine-keyhole limpet hemocyanin. Despite these deficits, immunization protected CRH-transgenic and wild-type mice equally well against lethal challenge with Streptococcus pneumoniae, an encapsulated Gram-positive bacterium known to require Ab-mediated opsonization for clearance. While IgG responses are severely depressed in these mice, IgM titers are only modestly decreased. This fairly robust IgM response may be sufficient to protect against S. pneumoniae. Additionally, while total leukocyte numbers are decreased in these mice, neutrophil numbers are increased. This increase in number of neutrophils may compensate for the depressed IgG response, allowing adequate host defense during chronic stress.

Original languageEnglish (US)
Pages (from-to)691-698
Number of pages8
JournalJournal of Immunology
Volume167
Issue number2
StatePublished - Jul 15 2001

Fingerprint

Corticotropin-Releasing Hormone
Genetic Models
Streptococcus pneumoniae
Antibody Formation
Lymphocytes
Transgenic Mice
Leukocyte Count
Immunoglobulin M
Immunization
Neutrophils
Immunoglobulin G
Immunoglobulin Class Switching
Phosphorylcholine
Gram-Positive Bacteria
Immunosuppressive Agents
Thymus Gland
B-Lymphocytes
Brain

ASJC Scopus subject areas

  • Immunology

Cite this

A genetic model of stress displays decreased lymphocytes and impaired antibody responses without altered susceptibility to Streptococcus pneumoniae. / Murray, Susan; Lallman, H. R.; Heard, A. D.; Rittenberg, Marvin; Stenzel-Poore, Mary.

In: Journal of Immunology, Vol. 167, No. 2, 15.07.2001, p. 691-698.

Research output: Contribution to journalArticle

@article{d24e5e1307b7431ab655762df2c28885,
title = "A genetic model of stress displays decreased lymphocytes and impaired antibody responses without altered susceptibility to Streptococcus pneumoniae",
abstract = "Stress pathways affect immune function, the most notable of these pathways being activation of the hypothalamic-pituitary-adrenal (HPA) axis. Although HPA activation has generally been relegated to an immunosuppressive role, recent evidence suggests that stress and HPA activation can be immunoenhancing in certain situations. To investigate specific effects of stress on immune function, we used a genetic model of chronic stress wherein transgenic mice overexpress corticotropin-releasing hormone (CRH), a primary mediator of the stress response. In these mice, CRH is overproduced in the brain, leading to chronic activation of the HPA axis. We found that CRH-transgenic mice have decreased leukocyte numbers in lymphoid compartments, with preferential loss of B lymphocytes. They also exhibit decreased Ab production and impaired isotype switching in response to immunization with a thymus-dependent Ag, phosphocholine-keyhole limpet hemocyanin. Despite these deficits, immunization protected CRH-transgenic and wild-type mice equally well against lethal challenge with Streptococcus pneumoniae, an encapsulated Gram-positive bacterium known to require Ab-mediated opsonization for clearance. While IgG responses are severely depressed in these mice, IgM titers are only modestly decreased. This fairly robust IgM response may be sufficient to protect against S. pneumoniae. Additionally, while total leukocyte numbers are decreased in these mice, neutrophil numbers are increased. This increase in number of neutrophils may compensate for the depressed IgG response, allowing adequate host defense during chronic stress.",
author = "Susan Murray and Lallman, {H. R.} and Heard, {A. D.} and Marvin Rittenberg and Mary Stenzel-Poore",
year = "2001",
month = "7",
day = "15",
language = "English (US)",
volume = "167",
pages = "691--698",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - A genetic model of stress displays decreased lymphocytes and impaired antibody responses without altered susceptibility to Streptococcus pneumoniae

AU - Murray, Susan

AU - Lallman, H. R.

AU - Heard, A. D.

AU - Rittenberg, Marvin

AU - Stenzel-Poore, Mary

PY - 2001/7/15

Y1 - 2001/7/15

N2 - Stress pathways affect immune function, the most notable of these pathways being activation of the hypothalamic-pituitary-adrenal (HPA) axis. Although HPA activation has generally been relegated to an immunosuppressive role, recent evidence suggests that stress and HPA activation can be immunoenhancing in certain situations. To investigate specific effects of stress on immune function, we used a genetic model of chronic stress wherein transgenic mice overexpress corticotropin-releasing hormone (CRH), a primary mediator of the stress response. In these mice, CRH is overproduced in the brain, leading to chronic activation of the HPA axis. We found that CRH-transgenic mice have decreased leukocyte numbers in lymphoid compartments, with preferential loss of B lymphocytes. They also exhibit decreased Ab production and impaired isotype switching in response to immunization with a thymus-dependent Ag, phosphocholine-keyhole limpet hemocyanin. Despite these deficits, immunization protected CRH-transgenic and wild-type mice equally well against lethal challenge with Streptococcus pneumoniae, an encapsulated Gram-positive bacterium known to require Ab-mediated opsonization for clearance. While IgG responses are severely depressed in these mice, IgM titers are only modestly decreased. This fairly robust IgM response may be sufficient to protect against S. pneumoniae. Additionally, while total leukocyte numbers are decreased in these mice, neutrophil numbers are increased. This increase in number of neutrophils may compensate for the depressed IgG response, allowing adequate host defense during chronic stress.

AB - Stress pathways affect immune function, the most notable of these pathways being activation of the hypothalamic-pituitary-adrenal (HPA) axis. Although HPA activation has generally been relegated to an immunosuppressive role, recent evidence suggests that stress and HPA activation can be immunoenhancing in certain situations. To investigate specific effects of stress on immune function, we used a genetic model of chronic stress wherein transgenic mice overexpress corticotropin-releasing hormone (CRH), a primary mediator of the stress response. In these mice, CRH is overproduced in the brain, leading to chronic activation of the HPA axis. We found that CRH-transgenic mice have decreased leukocyte numbers in lymphoid compartments, with preferential loss of B lymphocytes. They also exhibit decreased Ab production and impaired isotype switching in response to immunization with a thymus-dependent Ag, phosphocholine-keyhole limpet hemocyanin. Despite these deficits, immunization protected CRH-transgenic and wild-type mice equally well against lethal challenge with Streptococcus pneumoniae, an encapsulated Gram-positive bacterium known to require Ab-mediated opsonization for clearance. While IgG responses are severely depressed in these mice, IgM titers are only modestly decreased. This fairly robust IgM response may be sufficient to protect against S. pneumoniae. Additionally, while total leukocyte numbers are decreased in these mice, neutrophil numbers are increased. This increase in number of neutrophils may compensate for the depressed IgG response, allowing adequate host defense during chronic stress.

UR - http://www.scopus.com/inward/record.url?scp=0035879110&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035879110&partnerID=8YFLogxK

M3 - Article

C2 - 11441072

AN - SCOPUS:0035879110

VL - 167

SP - 691

EP - 698

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -