The macrophage pattern recognition scavenger receptors SR-A and CD36 protect against microbial induced pregnancy loss.
OBJECTIVE
Microbial products can act via stress-induced signaling cascades to link dysregulated endogenous microbiota to immune activation (e.g., macrophages) and pregnancy loss. Our previous studies demonstrated that mice deficient in the macrophage pattern recognition scavenger receptors, SR-A and CD36, are more susceptible to inflammatory complications including gut leakiness and experimental colitis. We hypothesized that bacterial penetration of the maternal mucosal surfaces and replication in embryonic fluids compromise the fetal status and can result in miscarriage.


METHODS
Eighty pregnant ICR and SR-A/CD36-deficient mice were injected via tail vein or intraperitoneally with commensal bacteria (Streptococcus cricetus and/or Actinobacillus sp.) or sham controls. Dams were monitored daily for physical distress, pain and abortion.


RESULTS
Dams injected with single dose bacterial inoculum did not develop clinical symptoms. Day old pups injected with bacteria developed internal focal abscesses, lost weight but recovered after 1 week. Dams receiving a second bacterial inoculum delivered dead fetuses. However, SR-A/CD36-deficnet dams demonstrated 100% fetal death via aborted fetuses, and significant up-regulation of the proinflammatory markers (IL-6, serum Amyloid A) 24-74 h after single inoculum.


CONCLUSIONS
These data indicate that macrophage scavenger receptors are required for the fetal protection against microbial attack and support that maternal transfer of innate immunity contributes to this protection.
Oz
Helieh S
HS
Center for Oral Health Research, MN310 College of Dentistry and Internal Medicine, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA. Helieh.oz@uky.edu
Ebersole
Jeffery L
JL
de Villiers
Willem J S
WJ
D000022:Abortion, Spontaneous / Q000209:etiology / Q000382:microbiology; D000818:Animals; D001424:Bacterial Infections / Q000150:complications*; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology*; D005260:Female; D006736:Horses; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy / Q000276:immunology*; D011251:Pregnancy Complications, Infectious; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
D018955:CD36 Antigens; D051117:Scavenger Receptors, Class A