Virus-Induced Type I Interferon Deteriorates Control of Systemic Pseudomonas Aeruginosa Infection.
BACKGROUND
Type I interferon (IFN-I) predisposes to bacterial superinfections, an important problem during viral infection or treatment with interferon-alpha (IFN-α). IFN-I-induced neutropenia is one reason for the impaired bacterial control; however there is evidence that more frequent bacterial infections during IFN-α-treatment occur independently of neutropenia.


METHODS
We analyzed in a mouse model, whether Pseudomonas aeruginosa control is influenced by co-infection with the lymphocytic choriomeningitis virus (LCMV). Bacterial titers, numbers of neutrophils and the gene-expression of liver-lysozyme-2 were determined during a 24 hours systemic infection with P. aeruginosa in wild-type and Ifnar(-/-) mice under the influence of LCMV or poly(I:C).


RESULTS
Virus-induced IFN-I impaired the control of Pseudomonas aeruginosa. This was associated with neutropenia and loss of lysozyme-2-expression in the liver, which had captured P. aeruginosa. A lower release of IFN-I by poly(I:C)-injection also impaired the bacterial control in the liver and reduced the expression of liver-lysozyme-2. Low concentration of IFN-I after infection with a virulent strain of P. aeruginosa alone impaired the bacterial control and reduced lysozyme-2-expression in the liver as well.


CONCLUSIONS
We found that during systemic infection with P. aeruginosa Kupffer cells quickly controlled the bacteria in cooperation with neutrophils. Upon LCMV-infection this cooperation was disturbed.
Institute of Immunology, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
Katja
K
Merches
Vishal
V
Khairnar
Torben
T
Knuschke
Namir
N
Shaabani
Nadine
N
Honke
Vikas
V
Duhan
Mike
M
Recher
Alexander A
AA
Navarini
Cornelia
C
Hardt
Dieter
D
Häussinger
Burkhard
B
Tümmler
Erich
E
Gulbins
Anthony H
AH
Futerman
Daniel
D
Hoffmann
Florian
F
Lang
Philipp A
PA
Lang
Astrid M
AM
Westendorf
Karl S
KS
Lang
D000818:Animals; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects; D007370:Interferon Type I / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000187:drug effects / Q000502:physiology*; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000378:metabolism; D009503:Neutropenia / Q000276:immunology / Q000473:pathology; D011070:Poly I-C / Q000494:pharmacology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014774:Virulence / Q000187:drug effects
D007370:Interferon Type I; D009113:Muramidase; D011070:Poly I-C