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

Research output: Contribution to journalArticle

  • External authors:
  • Sharon Campbell
  • Johanna Knipper
  • Conor Finlay
  • Nicola Logan
  • Carlos M Minutti
  • Matthias Mack
  • Stephen Jenkins
  • Matthew Taylor

Abstract

Both TH2-dependent helminth killing and suppression of the TH2 effector response have been attributed to macrophages (MΦ) activated by IL-4 (M(IL-4)). To investigate how M(IL-4) contribute to diverse infection outcomes, the MΦ 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 MΦ (resMΦ) 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 resMΦ population, confirming local proliferation as the driver of resMΦ expansion. Significantly less resMΦ 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.

Bibliographical metadata

Original languageEnglish
Article number30947
JournaleLife
Volume7
Issue numbere30947
DOIs
StatePublished - 4 Jan 2018