Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes.
BACKGROUND
Human monocyte inflammatory responses differ between virulent and attenuated Francisella infection.


RESULTS
A mixed infection model showed that the virulent F. tularensis Schu S4 can attenuate inflammatory cytokine responses to the less virulent F. novicida in human monocytes.


CONCLUSIONS
F. tularensis dampens inflammatory response by an active process.


CONCLUSIONS
This suppression may contribute to enhanced pathogenicity of F. tularensis. Francisella tularensis is a Gram-negative facultative bacterium that can cause the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. Previous work has shown that monocytes infected with highly virulent F. tularensis subsp. tularensis strain Schu S4 responded with a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes and cytokine production in comparison to those infected with the less virulent related F. novicida. However, it has been unclear whether the virulent Schu S4 was merely evading or actively suppressing monocyte responses. By using mixed infection assays with F. tularensis and F. novicida, we show that F. tularensis actively suppresses monocyte pro-inflammatory responses. Additional experiments show that this suppression occurs in a dose-dependent manner and is dependent upon the viability of F. tularensis. Importantly, F. tularensis was able to suppress pro-inflammatory responses to earlier infections with F. novicida. These results lend support that F. tularensis actively dampens human monocyte responses and this likely contributes to its enhanced pathogenicity.
Integrated Biomedical Graduate Program, The Ohio State University Columbus, OH, USA.
Devyn D
DD
Gillette
Department of Microbial Infection and Immunity, The Ohio State University Columbus, OH, USA ; Center for Microbial Interface Biology, The Ohio State University Columbus, OH, USA.
Heather M
HM
Curry
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University Columbus, OH, USA.
Thomas
T
Cremer
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University Columbus, OH, USA.
David
D
Ravneberg
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University Columbus, OH, USA.
Kavin
K
Fatehchand
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University Columbus, OH, USA.
Prexy A
PA
Shah
Center for Microbial Interface Biology, The Ohio State University Columbus, OH, USA ; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University Columbus, OH, USA.
Mark D
MD
Wewers
Department of Microbial Infection and Immunity, The Ohio State University Columbus, OH, USA ; Center for Microbial Interface Biology, The Ohio State University Columbus, OH, USA.
Larry S
LS
Schlesinger
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University Columbus, OH, USA.
Jonathan P
JP
Butchar
Center for Microbial Interface Biology, The Ohio State University Columbus, OH, USA ; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University Columbus, OH, USA.
Susheela
S
Tridandapani
Center for Microbial Interface Biology, The Ohio State University Columbus, OH, USA ; Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University Columbus, OH, USA.
Mikhail A
MA
Gavrilin
D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005604:Francisella tularensis / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D050296:Microbial Viability / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D014406:Tularemia / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D014774:Virulence
D016207:Cytokines
Francisella; cytokines; innate immunity; monocytes; signal transduction