Induced eosinophilia and mastocytosis are found in the intestinal

Induced eosinophilia and mastocytosis are found in the intestinal tract of IL-5 Tg mice undergoing a primary N. brasiliensis infection and relatively few larvae or worms can be recovered (69,75,76). The intestinal-stage parasites recovered from IL-5 Tg mice generally fail to localize in the preferred anterior third of the duodenum, are smaller than those from WT hosts and produce few eggs (64). Wild-type FVB/N mice also support few intestinal N. brasiliensis

larvae or worms at any stage of a primary infection (77). In none of the many host strains and genetic variants used in our studies have we seen strong inflammatory responses in the lungs 24–48 h pi., when most of the larvae are present (65,69,75,77). Intense inflammatory responses are evident 4–6 days post-primary infection and these may be focused on a few remaining larvae or larval sheaths, although a component of this inflammation may also reflect physical damage to the tissues caused by larval migration (65). Much has been made of this later response by other researchers, but it is important to understand that most larvae have migrated from the lungs to the gut by the end

of day 3 and Venetoclax concentration so at least in primary infections, it is not this stage of inflammation that is larvicidal or inhibitory to further development and colonization. Leucocytes are in fact very scarce in the lungs during the period when larvae are present, with just a small number of cells of macrophage-like appearance that are generally not closely associated with the parasite (65). The late pulmonary inflammatory response may be important for priming for adaptive

immunity and perhaps in limiting tissue damage, though the latter seems less likely. A strong inflammatory response with activation of potent effector cells in the lungs may be counterproductive for both parasite and host. It is worth noting that the means through which this early lung inflammation is prevented should provide for useful insights reaching beyond parasite immunology. We have some evidence that eosinophils and other leucocytes that accumulate in the gut may damage parasites at this site (69), but N. brasiliensis larvae are probably most vulnerable to attack earlier in the migratory pathway. In primary infections of IL-5 Tg (65) and WT FVB/N mice (77) and in secondary infections of WT CBA/Ca, BALB/c and C57BL/6 mice (69,75,76), larvae are trapped or damaged in the pre-lung phase of the migratory pathway. In primary infections of IL-5 Tg hosts, significant numbers of larvae are either trapped in the skin or migration to the lungs is prevented or delayed (65). Larvae that do manage to migrate to the lungs of IL-5 Tg mice are significantly smaller and paler than those recovered from WT mice (65). Conversely, more larvae can be recovered from the lungs of the IL-5−/− and ΔdblGATA deletion mutant strains in both primary and secondary infections (69).

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