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2015 ; 83
(12
): 4617-29
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English Wikipedia
Pulmonary immunostimulation with MALP-2 in influenza virus-infected mice
increases survival after pneumococcal superinfection
#MMPMID26371127
Reppe K
; Radünzel P
; Dietert K
; Tschernig T
; Wolff T
; Hammerschmidt S
; Gruber AD
; Suttorp N
; Witzenrath M
Infect Immun
2015[Dec]; 83
(12
): 4617-29
PMID26371127
show ga
Pulmonary infection with influenza virus is frequently complicated by bacterial
superinfection, with Streptococcus pneumoniae being the most prevalent causal
pathogen and hence often associated with high morbidity and mortality rates.
Local immunosuppression due to pulmonary influenza virus infection has been
identified as a major cause of the pathogenesis of secondary bacterial lung
infection. Thus, specific local stimulation of the pulmonary innate immune system
in subjects with influenza virus infection might improve the host defense against
secondary bacterial pathogens. In the present study, we examined the effect of
pulmonary immunostimulation with Toll-like receptor 2 (TLR-2)-stimulating
macrophage-activating lipopeptide 2 (MALP-2) in influenza A virus (IAV)-infected
mice on the course of subsequent pneumococcal superinfection. Female C57BL/6N
mice infected with IAV were treated with MALP-2 on day 5 and challenged with S.
pneumoniae on day 6. Intratracheal MALP-2 application increased proinflammatory
cytokine and chemokine release and enhanced the recruitment of leukocytes, mainly
neutrophils, into the alveolar space of IAV-infected mice, without detectable
systemic side effects. Local pulmonary instillation of MALP-2 in IAV-infected
mice 24 h before transnasal pneumococcal infection considerably reduced the
bacterial number in the lung tissue without inducing exaggerated inflammation.
The pulmonary viral load was not altered by MALP-2. Clinically, MALP-2 treatment
of IAV-infected mice increased survival rates and reduced hypothermia and body
weight loss after pneumococcal superinfection compared to those of untreated
coinfected mice. In conclusion, local immunostimulation with MALP-2 in influenza
virus-infected mice improved pulmonary bacterial elimination and increased
survival after subsequent pneumococcal superinfection.
|Animals
[MESH]
|Coinfection
[MESH]
|Female
[MESH]
|Hypothermia/prevention & control
[MESH]
|Immunity, Innate
[MESH]
|Immunization
[MESH]
|Immunologic Factors/*pharmacology
[MESH]
|Influenza A Virus, H1N1 Subtype/drug effects/immunology/pathogenicity
[MESH]