Myeloid cell recruitment versus local proliferation differentiates susceptibility from resistance to filarial infection

Both T(H)2-dependent helminth killing and suppression of the T(H)2 effector response have been attributed to macrophages (M Phi) activated by IL-4 (M(IL-4)). To investigate how M(IL-4) contribute to diverse infection outcomes, the MO compartment of susceptible BALB/c mice and more resistant C57BL/6 mice was profiled during infection of the pleural cavity with the filarial nematode, Litomosoides sigmodontis. C57BL/6 mice exhibited a profoundly expanded resident M Phi(resM Phi) population, which was gradually replenished from the bone marrow in an age dependent manner. Infection status did not alter the bone-marrow derived contribution to the resM Phi population, confirming local proliferation as the driver of resM Phi expansion. Significantly less resM Phi expansion was observed in the susceptible BALB/c strain, which instead exhibited an influx of monocytes that assumed an immunosuppressive PD-L2(+) phenotype. Inhibition of monocyte recruitment enhanced nematode killing. Thus, the balance of monocytic vs. resident M(IL-4) numbers varies between inbred mouse strains and impacts infection outcome.