Effects of repeated respiratory syncytial virus infections on pulmonary dendritic cells in a murine model of allergic asthma.
BACKGROUND
Primary and secondary respiratory syncytial virus (RSV) infection differentially regulates preexisting allergic airway inflammation.


OBJECTIVE
The present study was designed to determine the effects of primary and secondary low-grade RSV infections on pulmonary dendritic cell (DC) functions.


METHODS
Eight groups of BALB/c mice were used: one group each for control primary and secondary sensitization, primary and secondary sensitization to Dermatophagoides farinae (Derf) allergen, primary and secondary infection with RSV, and primary and secondary sensitization to Derf plus infection with RSV. CD11c+ pulmonary DCs were isolated from these mice and then transferred to naïve mice followed by intranasal Derf challenge. Furthermore, either anti-IL-12 monoclonal antibody (alphaIL-12 mAb) or anti-IL-10 (alphaIL-10) mAb were injected into donor mice after Derf challenge and during RSV infection to determine the involvement of IL-12 and IL-10.


RESULTS
Primary RSV infection failed to induce polarization in DCs since it failed to induce IL-10 and IL-12 production in Derf-sensitized donor lung. In contrast, secondary RSV infection significantly enhanced IL-12 production from Derf-sensitized donor lung, thereby enhancing both Th1 and Th2 responses. During RSV infection, alphaIL-12 but not alphaIL-10 mAb treatment blocked these immunological effects.


CONCLUSIONS
Via IL-12, DCs may play a critical role in shifting the immune response in this experimental model of repeated respiratory viral infection in allergic asthma.
Hirose
Hiroko
H
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Matsuse
Hiroto
H
Fukahori
Susumu
S
Tsuchida
Tomoko
T
Tomari
Shinya
S
Kawano
Tetsuya
T
Fukushima
Chizu
C
Mizuta
Yohei
Y
Kohno
Shigeru
S
D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity*
D039741:Antigens, Dermatophagoides; D018664:Interleukin-12