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.
Highlights
Litomosoides sigmodontis is a rodent filarial nematode which is used to model the host response to infection with filarial parasites of humans such as Onchocerca volvulus and Wuchereria bancrofti (Hoffmann et al, 2000)
We have previously reported that IL-4 induces the proliferative expansion of F4/80hi resident MF in the pleural cavity during L. sigmodontis infection, with minimal blood monocyte recruitment (Jenkins et al, 2011; Jenkins et al, 2013)
Due to the emergence of a Ly6C+ population within the pleural cavity of infected mice, cells expressing lower levels of F4/80 were further subdivided into F4/80loMHChiLy6C- monocyte-derived macrophages (F4/80lo) and recently recruited F4/80loMHClo-hiLy6C+ monocytes (Figure 1B)
Summary
Litomosoides sigmodontis is a rodent filarial nematode which is used to model the host response to infection with filarial parasites of humans such as Onchocerca volvulus and Wuchereria bancrofti (Hoffmann et al, 2000). In susceptible BALB/c mice parasites mature, mate and produce microfilariae that circulate in the bloodstream from ~day 55 post infection (pi). In contrast to BALB/c mice, C57BL/6 mice are considered resistant because the number of adult nematodes recoverable from the pleural cavity declines from ~day 22–55 and parasites do not reach sexual maturity or produce microfilariae (Hoffmann et al, 2000; Graham et al, 2005). The absence of IL-4, the central cytokine of type two immunity, renders C57BL/6 mice susceptible to L. sigmodontis infection, with blood microfilariae detectable at day 60 pi (Le Goff et al, 2002).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
