Yersinia-triggered arthritis in IL-12p40-deficient mice: relevant antigens and local expression of Toll-like receptor mRNA.
OBJECTIVE
To study the role of IL-12p40 at the onset of reactive arthritis (ReA) after Yersinia enterocolitica O:3 infection, and analyse relevant microbial antigens and articular expression of Toll-like receptor (TLR) mRNA.


METHODS
Wild-type C57BL/6 and IL-12p40-deficient (IL-12p40-/-) mice were orogastrically infected with Y. enterocolitica O:3. Early (day 3) and late (day 21) after infection, the number of bacteria were determined in Peyer's patches (PP), mesenteric lymph nodes (MLN), the spleen, and joints. Histological studies of joints were performed. Collagen-specific and anti-Yersinia antibodies were measured by enzyme-linked immunosorbent assay (ELISA). The presence of Yersinia antigens was studied by dot blot. Induction of articular mRNA of TLR2, TLR4, and tumour necrosis factor (TNF)-alpha was analysed by reverse transcription-polymerase chain reaction (RT-PCR). TNFalpha protein levels were measured by ELISA.


RESULTS
At day 3, bacterial recovery in PP, MLN, and spleen was significantly increased in IL-12p40-/- mice. Histopathological changes were observed in IL-12p40-/- mice at day 21 after infection, and correlated with higher antibody response against type II collagen. Although live bacteria could not be isolated at day 21 after infection, articular microbial components, especially from the outer membrane (OM), were detected. Moreover, intra-articular immunoglobulins to Yersinia antigens were significantly higher in IL-12p40-/- mice. Furthermore, mRNA levels for TLR2, TLR4 and TNFalpha, and TNFalpha protein were increased in joints from IL-12p40-/- mice.


CONCLUSIONS
We concluded that IL-12p40 influences the resistance against Yersinia-triggered ReA. Bacterial products such as Yersinia OM could contribute to the ReA by induction of articular TLR expression, which results in an inflammatory response in the joint.
Di Genaro
M S
MS
Laboratory of Microbiology, Faculty of Chemistry, Biochemistry and Pharmacy, National University of San Luis, 5700 San Luis, Argentina. sdigena@unsl.edu.ar
Cargnelutti
D E
DE
Castro
D O
DO
Eliçabe
R J
RJ
Gutiérrez
J V
JV
Correa
S G
SG
de Guzmán
A M S
AM
D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism; D000942:Antigens, Bacterial / Q000378:metabolism*; D016918:Arthritis, Reactive / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D053762:Interleukin-12 Subunit p40 / Q000172:deficiency / Q000502:physiology*; D007596:Joints / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015009:Yersinia Infections / Q000276:immunology*; D015008:Yersinia enterocolitica / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D053762:Interleukin-12 Subunit p40; D012333:RNA, Messenger; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha