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Fatal outcome of pandemic H1N1 2009 influenza virus infection is associated with
immunopathology and impaired lung repair, not enhanced viral burden, in pregnant
mice
#MMPMID21865394
Marcelin G
; Aldridge JR
; Duan S
; Ghoneim HE
; Rehg J
; Marjuki H
; Boon AC
; McCullers JA
; Webby RJ
J Virol
2011[Nov]; 85
(21
): 11208-19
PMID21865394
show ga
Pandemic A (H1N1) 2009 influenza virus (pH1N1) infection in pregnant women can be
severe. The mechanisms that affect infection outcome in this population are not
well understood. To address this, pregnant and nonpregnant BALB/c mice were
inoculated with the wild-type pH1N1 strain A/California/04/09. To determine
whether innate immune responses are associated with severe infection, we measured
the innate cells trafficking into the lungs of pregnant versus nonpregnant
animals. Increased infiltration of pulmonary neutrophils and macrophages strongly
correlated with an elevated mortality in pregnant mice. In agreement with this,
the product of nitric oxide (nitrite) and several cytokines associated with
recruitment and/or function of these cells were increased in the lungs of
pregnant animals. Surprisingly, increased mortality in pregnant mice was not
associated with higher virus load because equivalent virus titers and
immunohistochemical staining were observed in the nasal cavities or lungs of all
mice. To determine whether exacerbated inflammatory responses and elevated
cellularity resulted in lung injury, epithelial regeneration was measured. The
lungs of pregnant mice exhibited reduced epithelial regeneration, suggesting
impaired lung repair. Despite these immunologic alterations, pregnant animals
demonstrated equivalent percentages of pulmonary influenza virus-specific CD8(+)
T lymphocytes, although they displayed elevated levels of T-regulator lymphocytes
(Tregs) in the lung. Also, pregnant mice mounted equal antibody titers in
response to virus or immunization with a monovalent inactivated pH1N1
A/California/07/09 vaccine. Therefore, immunopathology likely caused by elevated
cellular recruitment is an implicated mechanism of severe pH1N1 infection in
pregnant mice.
|*Viral Load
[MESH]
|Animals
[MESH]
|CD8-Positive T-Lymphocytes/immunology
[MESH]
|Cytokines/analysis
[MESH]
|Disease Models, Animal
[MESH]
|Female
[MESH]
|Influenza A Virus, H1N1 Subtype/*immunology/*pathogenicity
[MESH]
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