Susceptible AKR/J mice demonstrate a Type 1 immune skew duringT. muris infection.
To prepare to assess basophil responses in a susceptible host, we first
validated that AKR/J mice are susceptible to T. muris and mount a
Type 1-skewed cytokine response to infection in our hands. AKR/J mice
were infected with 200 T. muris eggs orally. Worm burdens in the
ceca and cytokine gene expression in the proximal colon were analyzed at
day (d) 0 (naïve), 7, 14, 19 and 35 p.i. (Fig. 1A). These time points
were selected based on the T. muris life cycle and the kinetics
of the immune response that expels parasites in resistant mice (13).
Consistent with previous studies (9-13, 15), AKR/J mice did not expel
worms efficiently; the average worm burden decreased by d35 p.i., but
many AKR/J mice retained worms out to this timepoint (Fig. 1B).
Likewise, consistent with prior reports showing a Type 1-skewed cytokine
response in T. muris -infected AKR/J mice (9-13, 15),
infection-induced expression of the Th1-associated cytokine Ifngin the colon was observed at all time points p.i. and was
~70-fold higher in T. muris -infected AKR/J mice
at d19 p.i. than in naïve mice (Fig. 1C). We did also observe a
significant increase in Il4 levels in the colon of mice at d19
and d35 p.i. compared to naïve mice (Fig. 1D), but no significant
infection-induced increase in Il13 expression (Fig. 1E). These
data validate that, in our hands, AKR/J mice cannot uniformly expelT. muris by d19 p.i. as C57BL/6 mice can (9-13, 15), associated
with a skew towards Type 1 inflammation.
We next assessed various parameters of the host immune response
associated with granulocyte, specifically basophil, responses. We
observed a robust increase in colonic expression of Fcer1a , which
encodes for the high-affinity IgE receptor that is expressed on
basophils and mast cells (20-23, 29), in the colon of mice at d19 and
d35 p.i. with T. muris compared to naïve mice (Fig. 1F). We also
observed increased serum IgE upon infection, though this increase was
not statistically significant (Fig. S1A). As Fcer1a expression
and IgE levels are not indicative of basophil-specific activation, we
further quantified the expression of Mcpt8 , a basophil-specific
protease (27, 32, 33). Mcpt8 levels in the colon were
significantly increased in infected mice at d14, d19, and d35 p.i
compared to levels in naïve mice (Fig. 1G). Together, these data suggest
that basophils and potentially also mast cells that expressFcer1a for IgE binding are either activated or increased in
number in susceptible AKR/J mice during T. muris infection,
despite the presence of a Type 1-skewed inflammatory environment.