Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses

Timothy P. Welliver, Roberto Garofalo, Yashoda Hosakote Madaiah, Karen H. Hintz, Luis Avendano, Katherine Sanchez, Luis Velozo, Hasan Jafri, Susana Chavez-Bueno, Pearay L. Ogra, LuAnn McKinney, Jennifer L. Reed, Robert C. Welliver

Research output: Contribution to journalArticle

260 Citations (Scopus)

Abstract

Background. Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI. Methods. We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more-severe illness. We analyzed lung tissue from infants with fatal cases of RSV and influenza virus LRTI to determine the types of inflammatory cells present. Autopsy tissues were studied for the lymphotoxin granzyme and the apoptosis marker caspase 3. Results. Quantities of lymphocyte-derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza virus, rather than RSV, infection. Lung tissues from infants with fatal RSV and influenza virus LRTI demonstrated an extensive presence of viral antigen and a near absence of CD8-positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis. Conclusions. Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis.

Original languageEnglish (US)
Pages (from-to)1126-1136
Number of pages11
JournalJournal of Infectious Diseases
Volume195
Issue number8
DOIs
StatePublished - Apr 15 2007

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Respiratory Syncytial Viruses
Orthomyxoviridae
Respiratory System
Respiratory Tract Infections
Lymphocytes
Lung
Respiratory Syncytial Virus Infections
Cytokines
CD8-Positive T-Lymphocytes
Apoptosis
Granzymes
Lymphotoxin-alpha
Viral Antigens
Adaptive Immunity
Chemokines
Caspase 3
Natural Killer Cells
Autopsy

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. / Welliver, Timothy P.; Garofalo, Roberto; Hosakote Madaiah, Yashoda; Hintz, Karen H.; Avendano, Luis; Sanchez, Katherine; Velozo, Luis; Jafri, Hasan; Chavez-Bueno, Susana; Ogra, Pearay L.; McKinney, LuAnn; Reed, Jennifer L.; Welliver, Robert C.

In: Journal of Infectious Diseases, Vol. 195, No. 8, 15.04.2007, p. 1126-1136.

Research output: Contribution to journalArticle

Welliver, Timothy P. ; Garofalo, Roberto ; Hosakote Madaiah, Yashoda ; Hintz, Karen H. ; Avendano, Luis ; Sanchez, Katherine ; Velozo, Luis ; Jafri, Hasan ; Chavez-Bueno, Susana ; Ogra, Pearay L. ; McKinney, LuAnn ; Reed, Jennifer L. ; Welliver, Robert C. / Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses. In: Journal of Infectious Diseases. 2007 ; Vol. 195, No. 8. pp. 1126-1136.
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T1 - Severe human lower respiratory tract illness caused by respiratory syncytial virus and influenza virus is characterized by the absence of pulmonary cytotoxic lymphocyte responses

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AU - Garofalo, Roberto

AU - Hosakote Madaiah, Yashoda

AU - Hintz, Karen H.

AU - Avendano, Luis

AU - Sanchez, Katherine

AU - Velozo, Luis

AU - Jafri, Hasan

AU - Chavez-Bueno, Susana

AU - Ogra, Pearay L.

AU - McKinney, LuAnn

AU - Reed, Jennifer L.

AU - Welliver, Robert C.

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AB - Background. Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI. Methods. We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more-severe illness. We analyzed lung tissue from infants with fatal cases of RSV and influenza virus LRTI to determine the types of inflammatory cells present. Autopsy tissues were studied for the lymphotoxin granzyme and the apoptosis marker caspase 3. Results. Quantities of lymphocyte-derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza virus, rather than RSV, infection. Lung tissues from infants with fatal RSV and influenza virus LRTI demonstrated an extensive presence of viral antigen and a near absence of CD8-positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis. Conclusions. Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis.

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