Influence of platelet-activating factor receptor (PAFR) on Brucella abortus infection: implications for manipulating the phagocytic strategy of B. abortus.
BACKGROUND
Brucella abortus is an intracellular pathogen which can infect and persist in host cells through multiple interactions. Above all, its interaction to host cell receptor is important to understand the pathogenic mechanisms of B. abortus. Accordingly, we demonstrated that platelet-activating factor receptor (PAFR) affects host cell response against B. abortus infection.


RESULTS
First of all, B. abortus infection to macrophage induces secretion of platelet-activating factor (PAF), which is a PAFR agonist. The stimulation of PAFR by PAF remarkably increases B. abortus uptake into macrophages. It induces Janus kinase 2 (JAK2) and p38α phosphorylation, indicating that PAFR-mediated activation of JAK2 signaling leads to enhanced uptake of B. abortus. Moreover, the dynamics of F-actin polymerization revealed that PAFR-mediated B. abortus uptake is related with the reorganization of F-actin and JAK2. Upon B. abortus phagocytosis, reduced PAFR in the membrane and subsequently increased levels of PAFR colocalization with endosomes were observed which indicate that B. abortus uptake into macrophages allowed PAFR trafficking to endosomes.


CONCLUSIONS
This study demonstrated that PAFR has a compelling involvement in B. abortus uptake as a promoter of phagocytosis, which is associated with JAK2 activation. Thus, our findings establish a novel insight into a receptor-related phagocytic mechanism of B. abortus.
Animal and Plant Quarantine Agency, Anyang, Gyeonggi-do, 430-757, Republic of Korea.
Jin Ju
JJ
Lee
Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
Hannah Leah
HL
Simborio
Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
Alisha Wehdnesday Bernardo
AW
Reyes
Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
Huynh Tan
HT
Hop
Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
Lauren Togonon
LT
Arayan
Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
Hu Jang
HJ
Lee
Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
Wongi
W
Min
Animal and Plant Quarantine Agency, Anyang, Gyeonggi-do, 430-757, Republic of Korea.
Moon
M
Her
College of Veterinary Medicine, Kyungpook National University, Daegu, 702-701, Republic of Korea.
Man Hee
MH
Rhee
Department of Veterinary Public Health, Faculty of Agriculture, Yamaguchi University, Yamaguchi, 753-8515, Japan.
Masahisa
M
Watarai
Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, 660-701, Republic of Korea.
Hong Hee
HH
Chang
Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju, 660-701, Republic of Korea. kimsuk@gnu.ac.kr.|Institute of Agriculture and Life Science, Gyeongsang National University, Jinju, 660-701, Republic of Korea. kimsuk@gnu.ac.kr.
Suk
S
Kim
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002003:Brucella abortus / Q000378:metabolism / Q000472:pathogenicity*; D002006:Brucellosis / Q000378:metabolism / Q000382:microbiology; D011992:Endosomes / Q000378:metabolism; D054884:Host-Pathogen Interactions; D053614:Janus Kinase 2 / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology / Q000276:immunology* / Q000382:microbiology*; D051379:Mice; D010587:Phagocytosis; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D000067996:RAW 264.7 Cells; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2
B. abortus; JAK2; Phagocytosis; Platelet-activating factor receptor