The mucosal response of hamsters to a low-intensity superimposed secondary infection with the hookworm Ancylostoma ceylanicum

Abstract

An experiment was conducted to assess the mucosal response to low-dose superimposed challenge with Ancylostoma ceylanicum. Hamsters were assigned to five treatment groups (1-5 respectively): naïve controls; primary immunizing infection controls; challenge controls; immunized, anthelmintic-treated, challenged group; immunized, superimposed challenge group. Group 4 hamsters were resistant to challenge, whereas most of the challenge inoculum larvae established in Group 5. Villus height and crypt depth measurements were initially markedly divergent between these two groups but over time post-challenge (pc) values for both parameters drew nearer and by day 31 pc they were indistinguishable. The greatest change was experienced by Group 4 which showed increasing inflammation and gut pathology during the challenge infection. Mitotic activity in crypts and mast cell counts in the mucosa were highest in Group 5 on day 10 pc, but there was little to distinguish between Groups 4 and 5 by day 31 pc. Goblet cell, eosinophil and Paneth cell counts were very similar throughout in both groups but, in the case of Paneth cells, they were consistent with a possible role in protective immunity to challenge. Some adult worms survived throughout the period of intense inflammation, emphasizing their tremendous resilience and resistance to mucosal host protective responses.

The mucosal response of hamsters exposed to weekly repeated infections with the hookwormAncylostoma ceylanicum

“…This concurs with the results of a challenge experiment in which much higher eosinophil levels were recorded on days 10 and 31 after infection, reaching in excess of 500 eosinophils/mm 2 , compared with days 73 and 94, by which time the eosinophil response had declined to levels of between 200 and 300 cells/mm 2 (Alkazmi & Behnke, 2010), a pattern that is not dissimilar to that observed here. A very similar pattern was reported also by Alkazmi & Behnke (2011) in another challenge experiment, so quite clearly the intense levels of eosinophil infiltration observed early during primary exposure, reaching in excess of 600 cells/mm 2 , fall with time in these chronic infections. The marked contrast, then, with repeatedly infected animals, where eosinophil levels stayed elevated, at over 700 cells/mm 2 even 10 weeks after the first dose of larvae, may reflect a response to the continued stimulation of the mucosa by the arrival of fresh larvae.…”

“…Second, a consistent finding of our experiments with A. ceylanicum in hamsters has been the decline in Paneth cells after single-pulse infections (Elphick & Mahida, 2005; Alkazmi et al , 2008; Alkazmi & Behnke, 2010, 2011). We found that after clearance of worms, and also after subsequent challenge infection, there was a marked rebound effect, with Paneth cell numbers reaching much higher levels than in naïve controls, and this coincided with loss of incoming larvae in the first 2 weeks of the challenge infection (Alkazmi et al , 2008; Alkazmi & Behnke, 2010).…”

Hookworm virulence factors: making the most of the host

“…Despite of these intense changes, some adult worms survive for lengthy periods of time in this abnormal, inflamed environment in both primary and challenge infections in hamsters. At the same time, hamsters are capable to sustain and tolerate these intestinal alterations and mucosal inflammatory response for several weeks and, after removal of the adult worms, rapidly bounce back to normal [105].…”

Slow cycling intestinal stem cell and Paneth cell responses to Trichinella spiralis infection

“…Currently, there is limited information regarding stem cell responses during distinct stages (initiation, progression, repair and resolution) of inflammatory responses. There is also significant interest in the role of Paneth cells in the pathogenesis of chronic inflammatory diseases such as Crohn's disease (11) and in chronic nematode infections such as those caused by human hookworms (12,13).…”