The kinetics of cellular and humoral immune responses of common carp to presporogonic development of the myxozoan Sphaerospora molnari

Abstract

Background Sphaerospora molnari is a myxozoan parasite causing skin and gill sphaerosporosis in common carp ( Cyprinus carpio ) in central Europe. For most myxozoans, little is known about the early development and the expansion of the infection in the fish host, prior to spore formation. A major reason for this lack of information is the absence of laboratory model organisms, whose life-cycle stages are available throughout the year. Results We have established a laboratory infection model for early proliferative stages of myxozoans, based on separation and intraperitoneal injection of motile and dividing S. molnari stages isolated from the blood of carp. In the present study we characterize the kinetics of the presporogonic development of S. molnari , while analyzing cellular host responses, cytokine and systemic immunoglobulin expression, over a 63-day period. Our study shows activation of innate immune responses followed by B cell-mediated immune responses. We observed rapid parasite efflux from the peritoneal cavity (< 40 hours), an initial covert infection period with a moderate proinflammatory response for about 1–2 weeks, followed by a period of parasite multiplication in the blood which peaked at 28 days post-infection (dpi) and was associated with a massive lymphocyte response. Our data further revealed a switch to a massive anti-inflammatory response (up to 1456-fold expression of il-10 ), a strong increase in the expression of IgM transcripts and increased number of IgM + B lymphocytes, which produce specific antibodies for the elimination of most of the parasites from the fish at 35 dpi. However, despite the presence of these antibodies, S. molnari invades the liver 42 dpi, where an increase in parasite cell number and indistinguishable outer cell membranes are indicative of effective exploitation and disguise mechanisms. From 49 dpi onwards, the acute infection changes to a chronic one, with low parasite numbers remaining in the fish. Conclusions To our knowledge, this is the first time myxozoan early development and immune modulation mechanisms have been analyzed along with innate and adaptive immune responses of its fish host, in a controlled laboratory system. Our study adds important information on host–parasite interaction and co-evolutionary adaptation of early metazoans (Cnidaria) with basic vertebrate (fish) immune systems and the evolution of host adaptation and parasite immune evasion strategies. Electronic supplementary material The online version of this article (10.1186/s13071-019-3462-3) contains supplementary material, which is available to authorized users.

Passive Immunization Delays Disease Outcome in Gilthead Sea Bream Infected With Enteromyxum leei (Myxozoa), Despite the Moderate Changes in IgM and IgT Repertoire

“…For instance, some parasites are known to induce hypergammaglobulinemia, resulting in a polyclonal expansion with significantly increased antibody titers but a limited proportion of parasite-spAbs. This has been reported for human and fish protozoan parasites, such as Trypanosoma cruzi (66) or Trypanoplasma borreli (67), but also in some myxozoan infections caused by Sphaerospora molnari (68) or Tetracapsuloides bryosalmonae (23). The current results, showing a significant increase in clonotype diversity for both IgM and IgT, together with previous findings on this host-parasite model (27,35), seem to indicate a similar strategy for E. leei.…”

Transcriptome of Sphaerospora molnari (Cnidaria, Myxosporea) blood stages provides proteolytic arsenal as potential therapeutic targets against sphaerosporosis in common carp

“…They are also associated with host hemoglobin degradation in blood feeding parasites, e.g. many parasitic helminths [65] and maybe the case for S. molnari which proliferates in host blood and interacts with erythrocytes [29]. The replacement of a stabilising asparagine close to the His active site of Sm_CL3 was also seen in a cathepsin L of the myxozoan Kudoa thyrsites.…”

“…1, [26,28,30]). Sphaerospora molnari is a parasite of the common carp in Central Europe with motile blood stages that provoke a strong immune response [29] and are a likely co-factor for developing Swim Bladder Inflammation [30]. S. molnari blood stages (SMBS) are prime targets for parasite intervention therapy, as they are 1) responsible for massive proliferation in the earliest stages of infection of fish, 2) freely circulating in the blood and any drug targeting the SMBS would not need to be applied to host tissue or taken up by host cells; 3) they are circulating in the blood for an extended period and therefore there is a longer window for application of anti-parasite therapies.…”

Genetic Diversity of Serine Protease Inhibitors in Myxozoan (Cnidaria, Myxozoa) Fish Parasites

“…The identities of parasite TAMs were confirmed using species-specific 18S rDNA PCR and DNA sequencing, according to Sipos et al [ 39 ]. S. molnari proliferative, presporogonic blood stages were collected from the laboratory lineage maintained by intraperitoneal infection of parasite blood stages into specific pathogen-free common carp ( Cyprinus carpio ) in the Laboratory of Fish Protistology of the Institute of Parasitology, Biology Centre of CAS, Ceske Budejovice, Czech Republic [ 41 ]. M. lieberkuehni sporogonic stages were collected from the urinary bladder of pike ( Esox lucius ) in Třeboň area, Czech Republic.…”