Immunity
Immune antagonism may explain negative associations between parasites
susceptible to similar immune responses or environments.C.hepaticum shows negative associations with S.dispersa ,
which may be due to Th1-type responses exhibited during earlyC.hepaticum infection (Kim, Joo, & Chung, 2007) negatively
impacting Sarcocystis sp. infection.
Immune antagonism may also explain the negative association betweenT.muris and S.obvelata . Similar associations are observed
in mice artificially infected with the pinworm Aspiculuris
teraptera , which suffered reduced T. muris burdens (Keeling,
1961). The steady increase in T. muris prevalence associated with
age and high prevalence of low-level infection in this population may be
indicators of T. muris establishing chronic infections, which are
characterised by immunosuppression of protective Th2 responses and
polarisation to a Th1 environment in infection models (Artis, Potten,
Else, Finkelman, & Grencis, 1999; Else, Hültner, & Grencis, 1992).
This is in contrast to T. muris infections observed in other wild
rodents, in which burdens increase with age (Behnke, Lewis, Zain, &
Gilbert, 1999), and Trichuris distributions observed in humans,
in which burdens spike during early life, then decrease to a steady low
level (Bundy, Cooper, Thompson, Didier, & Simmons, 1987; Faulkner et
al., 2002; Needham et al., 1992). S. obvelata prevalence shows no
significant association with age, indicating that parasite clearance and
possible reinfection could be the norm. Induction of Th2 responses byS. obvelata could disrupt the immunosuppressive environment
established by T. muris , negatively impacting its abundance
(Moreau & Chauvin, 2010).
Immune facilitation or suppression may contribute to the positive
association between C.hepaticum and Bartonella sp.Polarisation to a Th2 environment observed during some stages of theC.hepaticum life cycle (Kim et al., 2007) could reduce protective
immunity to microparasites, which are typically characterised by
Th1-type responses (Arvand, Ignatius, Regnath, Hahn, & Mielke, 2001;
Kabeya et al., 2007; Karem, Dubois, McGill, & Regnery, 1999). A
positive association between C. hepaticum and Bartonella
elizabethae was reported in the brown rat (Rattus norvegicus ),
though this was based upon an unusual increase in pathology observed in
one coinfected individual (Kamani, Akanbi, Baneth, Morrick, & Harrus,
2013).
Peripheral impacts of immunomodulation could be playing a role in the
association between C.hepaticum and T.muris . Jackson et al
(2009) found positive associations between C. hepaticum and the
intestinal nematode Heligmosomoides polygyrus in wild wood miceApodemus sylvaticus, associated with reduced innate immune
responses. In rats artificially infected with C.hepaticum , Th1/2
polarisation is observed, with IL-5 (Th2) increasing as the worms
matured, and IFNγ (Th1) peaking during egg deposition (Kim et al.,
2007). Systemic polarisation to a Th1 environment during C.
hepaticum egg deposition could improve survival of T. muris .
Moon et al (2017) observed a protective immune response to infection
against C. hepaticum and a similar hepatic nematodeClonorchis sinensis in laboratory rats, characterised by
eosinophilia and lymphocyte proliferation. The interaction observed in
this population may, therefore, alternatively be mediated by an
immunosuppressive effect on the part of T. muris , favouringC. hepaticum survival. (Kim et al., 2007).
Associations observed with ectoparasites are less well defined in this
population, and less well characterised from laboratory models.
Inflammation in the skin may contribute to protection against parasitic
arthropods (Moats, Baxter, Pate, & Watson, 2016), and the dermal tissue
has been recognised as a site of important immune activity (Kupper,
1990). Th2-type responses have been detected in response to ectoparasite
infection (Burgess et al., 2010; Wikel & Alarcon-Chaidez, 2001), which
may polarise away from the Th1-type response observed in earlyC.hepaticum infection, and contribute to a positive association
between C.hepaticum and mite burden. (Kim et al., 2007).
Pre-existing immune environments within the host, determined by factors
other than infection and not accounted for in this study, such as
genetics, predispose individuals to susceptibility to or protection
against infection. Cross-reactivity between antigens of different
nematode species has been observed in both mice and humans (Lillywhite,
Bundy, Didier, Cooper, & Bianco, 1991; Nieuwenhuizen et al., 2013;
Roach, Wakelin, Else, & Bundy, 1988), and so modulations to the immune
environment caused by one helminth may impact the survival of other
species.