Eosinophils mediate SIgA production triggered by TLR2 and TLR4 to control Ascaris suum infection in mice

Human ascariasis is the most prevalent but neglected tropical disease in the world, affecting approximately 450 million people. The initial phase of Ascaris infection is marked by larval migration from the host’s organs, causing mechanical injuries followed by an intense local inflammatory response, which is characterized mainly by neutrophil and eosinophil infiltration, especially in the lungs. During the pulmonary phase, the lesions induced by larval migration and excessive immune responses contribute to tissue remodeling marked by fibrosis and lung dysfunction. In this study, we investigated the relationship between SIgA levels and eosinophils. We found that TLR2 and TLR4 signaling induces eosinophils and promotes SIgA production during Ascaris suum infection. Therefore, control of parasite burden during the pulmonary phase of ascariasis involves eosinophil influx and subsequent promotion of SIgA levels. In addition, we also demonstrate that eosinophils also participate in the process of tissue remodeling after lung injury caused by larval migration, contributing to pulmonary fibrosis and dysfunction in re-infected mice. In conclusion, we postulate that eosinophils play a central role in mediating host innate and humoral immune responses by controlling parasite burden, tissue inflammation, and remodeling during Ascaris suum infection. Furthermore, we suggest that the use of probiotics can induce eosinophilia and SIgA production and contribute to controlling parasite burden and morbidity of helminthic diseases with pulmonary cycles.     

Zoite migration during infection: parasite adaptation to host defences

The apicomplexan parasite Eimeria tenella has evolved a number of strategies for migration into different compartments of the intestinal tissue during its life cycle. These migration events are associated intricately with pathogenesis and are currently of great interest to coccidiologists. Using evidence from in vivo studies and recent work on the dynamics of gut cell turnover, Peter Daszak suggests that E. tenella zoite migration might be viewed as parasite evolutionary adaptation to evade the host innate immune responses (resistance) and deal with the complex, dynamic nature of gut epithelial tissue.     

Neospora caninum excreted/secreted antigens trigger CC-chemokine receptor 5-dependent cell migration

Neospora caninum, the causative agent of neosporosis, is an obligate intracellular parasite considered to be a major cause of abortion in cattle throughout the world. Most studies concerning N. caninum have focused on life cycle, seroepidemiology, pathology and vaccination, while data on host-parasite interaction, such as host cell migration, mechanisms of evasion and dissemination of this parasite during the early phase of infection are still poorly understood. Here we show the ability of excreted/secreted antigens from N. caninum (NcESAs) to attract monocytic cells to the site of primary infection in both in vitro and in vivo assays. Molecules from the family of cyclophilins present on the NcESAs were shown to work as chemokine-like proteins and NcESA-induced chemoattraction involved G_i protein signaling and participation of CC-chemokine receptor 5 (CCR5). Additionally, we demonstrate the ability of NcESAs to enhance the expression of CCR5 on monocytic cells and this increase occurred in parallel with the chemotactic activity of NcESAs by increasing cell migration. These results suggest that during the first days of infection, N. caninum produces molecules capable of inducing monocytic cell migration to the sites of infection, which will consequently enhance initial parasite invasion and proliferation. Altogether, these results help to clarify some key features involved in the process of cell migration and may reveal virulence factors and therapeutic targets to control neosporosis.     

The anatomy and development of the rhizocephalan barnacle Clistosaccus paguri Lilljeborg and relation to its host pagurus bernhardus (L.)

The anatomy of all developmental stages of Clistosaccus paguri Lilljeborg including internal primordia only 200 μm across has been studied by conventional and ultrastructural techniques. The earliest primordia lack any roots and organs. A receptacle and ovary arise as separate structures. The colleteric gland develops by infolding of the mantle cavity epithelium. The primordium becomes external during a host intermoult. The externa is apparently female. It is proposed that male cyprids, through the integument, have implanted cells found in the mantle of the externa. These male cells travel through the mantle into the single receptacle, where they proceed with spermatogenesis. Externae lacking male cells will not grow. The larvae are released as cyprids, in which no preformed kentrogon is present. About half of the infected hosts carry more than one externa. Multiple externae are separate and may represent different invading female cyprids. C. paguri infects all sizes of its host, and castrates it. The effect of the parasite on the host is discussed. The life span of the parasite seems to be one year and the parasite population shows an annual cycle.     

Development of a gregarious ectoparasitoid, Euplectrus separatae (Hymenoptera; Hymenoptera: Eulophidae), that parasitizes Pseudaletia separata (Lepidoptera: Noctuidae)

Euplectrus separatae is a gregarious ectoparasitoid that parasitizes Pseudaletia separata during its third to sixth (last) instars. The eggs of the parasitoid are fixed on the integument of the host dorsolaterally with a hard substance like a piling driven into the integument by the female wasp at the time of oviposition. The first instar of the parasitoid, which hatches three days after oviposition is nourished by ingesting the hemolymph of the host, and ecdyses to the second stadium six days after oviposition. Many hemocytes and epidermal cells were found assembled under the piling and places where a parasitoid had attached its mouth, suggesting that the host had repaired the integument destroyed by the parasitoid. Botryoidal tissue, which stained well with hematoxylin, began to develop from four days after oviposition and became gradually larger with development. Botryoidal tissue appears to function as a secretory organ for thread and a storage organ for nutrients. Seven days after oviposition, the parasitoid larvae migrate down from the dorsal surface to the ventral side of the host. Just before descending they ecdyse to the third stadium and kill the host during their migration. If all parasitoid larvae were removed artificially from the host before they migrate, the host did not die. However, removing the parasitoids after they had started to migrate did not prevent the death of the host. Transmission electron microscopic (TEM) observation of salivary glands of a parasitoid larva before migrating revealed that the salivary gland was composed of cells that were rich in rough surfaced endoplasmic reticulum (rough-ER) with many ribosomes and cells that were filled with a lot of vacuoles just before their collapse. After moving from the host body, the parasitoid larvae doubled in weight by ingesting the tissue of the host and then spun a cocoon. Almost all host tissues were consumed for growth of the parasitoid, like an idiobiont parasitoid.     

Patterns of parasitism in monarch butterflies during the breeding season in eastern North America

1. Migratory behaviour can result in reduced prevalence of pathogens in host populations. Two hypotheses have been proposed to explain this relationship: (i) ‘migratory escape’, where migrants benefit from escaping pathogen accumulation in contaminated environments; and (ii) ‘migratory culling’, where the selective removal of infected individuals occurs during migration. 2. In the host–parasite system between the monarch butterfly (Danaus plexippus Linn.) and its obligate protozoan parasite Ophryocystis elektroscirrha (OE), there is evidence to support both hypotheses, particularly during the monarchs' autumn migration. However, these processes can operate simultaneously and could vary throughout the monarchs' annual migratory cycle. Assessing the relative strength for each hypothesis has not previously been done. 3. To evaluate both hypotheses, parasite infection prevalence was examined in monarchs sampled in eastern North America during April–September, and stable isotopes (δ²H, δ¹³C) were used to estimate natal origin and infer migration distance. There was stronger support for the migratory escape hypothesis, wherein infection prevalence increased over the breeding season and was higher at southern latitudes, where the breeding season tends to be longer compared with northern latitudes. Little support was found for the migratory culling hypothesis, as infection prevalence was similar whether monarchs travelled shorter or longer distances. 4. These results suggest that migration allows individuals to escape parasites not only during the autumn, as shown in previous work, but during the monarchs' spring and summer movements when they recolonise the breeding range. These results imply a potential fitness advantage to monarchs that migrate further north to exploit parasite‐free habitats.     

The induction of host cell autophagy triggers defense mechanisms against Trypanosoma cruzi infection in vitro

Trypanosoma cruzi causes Chagas disease, a neglected illness that affects millions of people worldwide, especially in Latin America. The balance between biochemical pathways triggered by the parasite and host cells response will ultimately define the progression of a life-threatening disease, justifying the efforts to understand cellular mechanisms for infection restrain. In this interaction, parasite and host cells are affected by different physiological responses as autophagy modulation, which could be under intense cellular stress, such as nutrient deprivation, hormone depletion, or infection. Autophagy is a constitutive pathway that leads to degradation of macromolecules and cellular structures and may induce cell death. In Trypanosoma cruzi infection, the relevance of host autophagy is controversial regarding in vitro parasite intracellular life cycle. In the present study, we evaluated host cell autophagy during T. cruzi infection in phagocytic and non-professional phagocytic cells. We described that the presence of the parasite increased the number of LC3 puncta, a marker for autophagy, in cardiac cells and peritoneal macrophages in vitro. The induction of host autophagy decreased infection in macrophages in early and late time-periods. We suggest that starved phagocytic cells reduced internalization, also confirmed by inert particles and dead trypomastigotes. Whereas, in cardiac cells, starvation-induced autophagy decreased lipid droplets and infection in later time-point, by reducing parasite differentiation/proliferation. In ATG5 knockout MEF cells, we confirmed our hypothesis of autophagy machinery activation during parasite internalization, increasing infection. Our data suggest that host autophagy downregulates T. cruzi infection through impairing parasite intracellular life cycle, reducing the infection in primary culture cells.     

Intensity-dependent mortality of Paracalliope novizealandiae (Amphipoda: Crustacea) infected by a trematode: experimental infections and field observations

The impact of parasitism on population dynamics and community structure of marine animals is an area of growing interest in marine ecology. The effect of a microphallid trematode, Maritrema novaezelandensis on the survival of its amphipod host, Paracalliope novizealandiae, was investigated by a laboratory study combined with data from field collections. In the laboratory, the effect of infection level on host mortality was investigated. Four groups of individuals were exposed to 0 (control), 5 (low), 25 (moderate) and 125 (high) cercariae, respectively, and their survival was monitored during a 10-day period. The distribution and migration of unencysted cercariae within the host were examined during dissections 6 and 48 h post infection. Parasite-induced mortality under field conditions was investigated by quantifying the relationship between parasite load and host body size. In the laboratory experiment, a highly significant decrease in host survival was observed for amphipods in the moderate and high infection groups relative to that of control amphipods. Parasite-induced mortality was most pronounced in the first two days post infection suggesting that the increased mortality is due to penetration of host cuticula and migration of cercariae within the host. Field data showed a monotonic increase in the mean parasite load with the body size of the amphipods, indicating that M. novaezelandensis does not severely affect P. novizealandiae-populations under normal field conditions. However, a decrease in the variance-to-mean ratio for the largest size-classes indicates that heavily infected individuals are removed from the population as predicted by the experimental infections. The results from the laboratory study in conjunction with our knowledge of the transmission strategy of the parasite emphasize the potential effect of M. novaezelandensis on its amphipod host population during episodes of high temperature causing the rapid and massive release of cercariae from snail intermediate hosts.     

The Actin Filament-Binding Protein Coronin Regulates Motility in Plasmodium Sporozoites

Parasites causing malaria need to migrate in order to penetrate tissue barriers and enter host cells. Here we show that the actin filament-binding protein coronin regulates gliding motility in Plasmodium berghei sporozoites, the highly motile forms of a rodent malaria-causing parasite transmitted by mosquitoes. Parasites lacking coronin show motility defects that impair colonization of the mosquito salivary glands but not migration in the skin, yet result in decreased transmission efficiency. In non-motile sporozoites low calcium concentrations mediate actin-independent coronin localization to the periphery. Engagement of extracellular ligands triggers an intracellular calcium release followed by the actin-dependent relocalization of coronin to the rear and initiation of motility. Mutational analysis and imaging suggest that coronin organizes actin filaments for productive motility. Using coronin-mCherry as a marker for the presence of actin filaments we found that protein kinase A contributes to actin filament disassembly. We finally speculate that calcium and cAMP-mediated signaling regulate a switch from rapid parasite motility to host cell invasion by differentially influencing actin dynamics.     

Virulence and virulence factors in Entamoeba histolytica,the agent of human amoebiasis

Human infections with Entamoeba histolytica sporadically become pathogenic, unknown triggers converting the parasite to its invasive phenotype. Parasite virulence results from complex host–parasite interactions implicating multiple amoebic and host factors, eliciting host defence responses and parasite resistance to stress caused by the host reactions and changing environments during tissue invasion.     

Trichobilharzia regenti: host immune response in the pathogenesis of neuroinfection in mice

Besides their natural bird hosts, Trichobilharzia regenti cercariae are able to penetrate skin of mammals, including humans. Experimental infections of mice showed that schistosomula of this species are able to avoid the immune response in skin of their non-specific mammalian host and escape the skin to migrate to the CNS. Schistosomula do not mature in mammals, but can survive in nervous tissue for several days post infection. Neuroinfections of specific bird hosts as well as accidental mammalian hosts can lead to neuromotor effects, for example, leg paralysis and thus this parasite serves as a model of parasite invasion of the CNS.Here, we show by histological and immunohistochemical investigation of CNS invasion of immunocompetent (BALB/c) and immunodeficient (SCID) mice by T. regenti schistosomula that the presence of parasites in the nervous tissue initiated an influx of immune cells, activation of microglia, astrocytes and development of inflammatory lesions. Schistosomula elimination in the tissue depended on the host immune status. In the absence of CD3+ T-cells in immunodeficient SCID mice, parasite destruction was slower than that in immunocompetent BALB/c mice. Axon injury and subsequent secondary demyelination in the CNS were associated with mechanical damage due to migration of schistosomula through the nervous tissue, and not by host immune processes. Immunoreactivity of the parasite intestinal content for specific antigens of oligodendrocytes/myelin and neurofilaments showed for the first time that schistosomula ingest the nervous tissue components during their migration.     

Trypanosoma cruzi utilizes the host low density lipoprotein receptor in invasion

Background

Trypanosoma cruzi, an intracellular protozoan parasite that infects humans and other mammalian hosts, is the etiologic agent in Chagas disease. This parasite can invade a wide variety of mammalian cells. The mechanism(s) by which T. cruzi invades its host cell is not completely understood. The activation of many signaling receptors during invasion has been reported; however, the exact mechanism by which parasites cross the host cell membrane barrier and trigger fusion of the parasitophorous vacuole with lysosomes is not understood.

Methodology/Principal Findings

In order to explore the role of the Low Density Lipoprotein receptor (LDLr) in T. cruzi invasion, we evaluated LDLr parasite interactions using immunoblot and immunofluorescence (IFA) techniques. These experiments demonstrated that T. cruzi infection increases LDLr levels in infected host cells, inhibition or disruption of LDLr reduces parasite load in infected cells, T. cruzi directly binds recombinant LDLr, and LDLr-dependent T. cruzi invasion requires PIP2/3. qPCR analysis demonstrated a massive increase in LDLr mRNA (8000 fold) in the heart of T. cruzi infected mice, which is observed as early as 15 days after infection. IFA shows a co-localization of both LDL and LDLr with parasites in infected heart.

Conclusions/Significance

These data highlight, for the first time, that LDLr is involved in host cell invasion by this parasite and the subsequent fusion of the parasitophorous vacuole with the host cell lysosomal compartment. The model suggested by this study unifies previous models of host cell invasion for this pathogenic protozoon. Overall, these data indicate that T. cruzi targets LDLr and its family members during invasion. Binding to LDL likely facilitates parasite entry into host cells. The observations in this report suggest that therapeutic strategies based on the interaction of T. cruzi and the LDLr pathway should be pursued as possible targets to modify the pathogenesis of disease following infection.     

Biology of the microsporidan parasite Pleistophora crangoni n. sp. in three species of crangonid sand shrimps

The microsporidium Pleistophora crangoni n. sp. is a common parasite of Crangon franciscorum, C. nigricauda, and C. stylirostris in the vicinity of Yaquina Bay, Oregon. Characteristics of the parasite are described. Skeletal muscle was the only host tissue infected. The seasonal prevalence and intensity of the parasite in crangonids are described, based on examination of 1556 C. franciscorum, 3877 C. nigricauda, and 1674 C. stylirostris collected at monthly intervals from June 1975 through June 1976. Prevalence in C. franciscorum and C. stylirostris increased through the autumn and reached winter peaks of 30.3 and 41.0%, respectively, then decreased in the spring. Prevalence in C. nigricauda remained below 8% through the year. Intensity increased with size of the shrimps in the three species. Infection experiments and field observations suggest that only very young shrimps are susceptible to infection during a relatively short period during the summer months. Following natural infection, the parasite spreads within the host, indicating repeated schizogonic cycles. Parasitic castration was indicated by the absence of gravid infected female shrimps and was confirmed by histological examination. Ovaries of infected shrimps did not develop beyond a very early stage. A shift in sex ratio toward females in infected shrimps indicates that the parasite may influence sex determination. Shrimps showed little cellular response to infection. Only rarely in heavily infected shrimps was encapsulation of parasite cysts observed; necrotic tissue was occasionally observed. Infected shrimps usually succumbed before uninfected shrimps when subjected to oxygen stress. The collection of infected shrimps that were unusually large may indicate that these individuals grew faster or lived longer than uninfected shrimps.     

Host specificity of avian haemosporidian parasites is unrelated among sister lineages but shows phylogenetic signal across larger clades

Parasites can vary in the number of host species they infect, a trait known as “host specificity”. Here we quantify phylogenetic signal—the tendency for closely related species to resemble each other more than distantly related species—in host specificity of avian haemosporidian parasites (genera Plasmodium, Haemoproteus and Leucocytozoon) using data from MalAvi, the global avian haemosporidian database. We used the genetic data (479 base pairs of cytochrome b) that define parasite lineages to produce genus level phylogenies. Combining host specificity data with those phylogenies revealed significant levels of phylogenetic signal while controlling for sampling effects; phylogenetic signal was higher when the phylogenetic diversity of hosts was taken into account. We then tested for correlations in the host specificity of pairs of sister lineages. Correlations were generally close to zero for all three parasite genera. These results suggest that while the host specificity of parasite sister lineages differ, larger clades may be relatively specialised or generalised.     

Does timing matter? How priority effects influence the outcome of parasite interactions within hosts

In nature, hosts are exposed to an assemblage of parasite species that collectively form a complex community within the host. To date, however, our understanding of how within-host–parasite communities assemble and interact remains limited. Using a larval amphibian host (Pacific chorus frog, Pseudacris regilla) and two common trematode parasites (Ribeiroia ondatrae and Echinostoma trivolvis), we experimentally examined how the sequence of host exposure influenced parasite interactions within hosts. While there was no evidence that the parasites interacted when hosts were exposed to both parasites simultaneously, we detected evidence of both intraspecific and interspecific competition when exposures were temporally staggered. However, the strength and outcome of these priority effects depended on the sequence of addition, even after accounting for the fact that parasites added early in host development were more likely to encyst compared to parasites added later. Ribeiroia infection success was reduced by 14 % when Echinostoma was added prior to Ribeiroia, whereas no such effect was noted for Echinostoma when Ribeiroia was added first. Using a novel fluorescent-labeling technique that allowed us to track Ribeiroia infections from different exposure events, we also discovered that, similar to the interspecific interactions, early encysting parasites reduced the encystment success of later arriving parasites by 41 %, which could be mediated by host immune responses and/or competition for space. These results suggest that parasite identity interacts with host immune responses to mediate parasite interactions within the host, such that priority effects may play an important role in structuring parasite communities within hosts. This knowledge can be used to assess host–parasite interactions within natural communities in which environmental conditions can lead to heterogeneity in the timing and composition of host exposure to parasites.     

Exocrine glands of Lepeophtheirus salmonis (Copepoda: Caligidae): Distribution,developmental appearance,and site of secretion

Exocrine glands of blood‐feeding parasitic copepods are believed to be important in host immune response modulation and inhibition of host blood coagulation, but also in the production of substances for integument lubrication and antifouling. In this study, we aimed to characterize the distribution of different types of salmon louse (Lepeophtheirus salmonis) exocrine glands and their site of secretion. The developmental appearance of each gland type was mapped and genes specifically expressed by glands were identified. Three types of tegumental (teg 1–3) glands and one labial gland type were found. The first glands to appear during development were teg 1 and teg 2 glands. They have ducts extending both dorsally and ventrally suggested to be important in lubricating the integument. Teg 1 glands were found to express two astacin metallopeptidases and a gene with fibronectin II domains, while teg 2 glands express a heme peroxidase. The labial glands were first identified in planktonic copepodids, with reservoirs that allows for storage of glandular products. The last gland type to appear during development was named teg 3 and was not seen before the preadult I stage when the lice become more virulent. Teg 3 glands have ducts ending ventrally at the host‐parasite contact area, and may secrete substances important for the salmon lice virulence. Salmon lice teg 3 and labial glands are thus likely to be especially important in the host‐parasite interaction. Proteins secreted from the salmon louse glands to its salmonid host skin or blood represents a potential interface where the host immune system can meet and elicit effective responses to sea lice antigens. The present study thus represents a fundamental basis for further functional studies and identification of possible vaccine candidates. J. Morphol. 277:1616–1630, 2016. © 2016 Wiley Periodicals, Inc.     

Population Genetics of Schistosoma japonicum within the Philippines Suggest High Levels of Transmission between Humans and Dogs

Background

Schistosoma japonicum, which remains a major public health problem in the Philippines and mainland China, is the only schistosome species for which zoonotic transmission is considered important. While bovines are suspected as the main zoonotic reservoir in parts of China, the relative contributions of various non-human mammals to S. japonicum transmission in the Philippines remain to be determined. We examined the population genetics of S. japonicum in the Philippines in order to elucidate transmission patterns across host species and geographic areas.

Methodology/Principal Findings

S. japonicum miracidia (hatched from eggs within fecal samples) from humans, dogs, pigs and rats, and cercariae shed from snail-intermediate hosts, were collected across two geographic areas of Samar Province. Individual isolates were then genotyped using seven multiplexed microsatellite loci. Wright''s F_ST values and phylogenetic trees calculated for parasite populations suggest a high frequency of parasite gene-flow across definitive host species, particularly between dogs and humans. Parasite genetic differentiation between areas was not evident at the definitive host level, possibly suggesting frequent import and export of infections between villages, although there was some evidence of geographic structuring at the snail–intermediate host level.

Conclusions/Significance

These results suggest very high levels of transmission across host species, and indicate that the role of dogs should be considered when planning control programs. Furthermore, a regional approach to treatment programs is recommended where human migration is extensive.     

5-Lipoxygenase is a key determinant of acute myocardial inflammation and mortality during Trypanosoma cruzi infection

This study provides evidence supporting the idea that although inflammatory cells migration to the cardiac tissue is necessary to control the growth of Trypanosoma cruzi, the excessive influx of such cells during acute myocarditis may be deleterious to the host. Production of lipid mediators of inflammation like leukotrienes (LTs) along with cytokines and chemokines largely influences the severity of inflammatory injury in response to tissue parasitism. T. cruzi infection in mice deficient in 5-lipoxygenase (5-LO), the enzyme responsible for the synthesis of LTs and other lipid inflammatory mediators, resulted in transiently increased parasitemia, and improved survival rate compared with WT mice. Myocardia from 5-LO^?/? mice exhibited reduced inflammation, collagen deposition, and migration of CD4⁺, CD8⁺, and IFN-γ-producer cells compared with WT littermates. Moreover, decreased amounts of TNF-α, IFN-γ, and nitric oxide synthase were found in the hearts of 5-LO^?/? mice. Interestingly, despite of early higher parasitic load, 5-LO^?/? mice survived, and controlled T. cruzi infection. These results show that efficient parasite clearance is possible in a context of moderate inflammatory response, as occurred in 5-LO^?/? mice, in which reduced myocarditis protects the animals during T. cruzi infection.     

Local and Systemic Effects on Inflammation during Eimeria nieschulzi Infection1

Rats infected with Eimeria nieschulzi, a coccidium that inhabits intestinal epithelium, have a lower basal inflammatory state in their intestinal mucosa eight days postinoculation as reflected by a drop in mucosal peroxidase activity and a decrease in the number of granulocytes in the lamina propria. The reduction of systemic inflammation in infected rats was assessed from a reduction in the formation of granulation tissue around a sterile cotton string implanted under the abdominal skin of the hosts. This reduced inflammatory response, both locally and systemically, occurs during the development of gamonts by the parasite and the release of oocysts from the host. These results plus the presence of normal or slightly elevated numbers of granulocytes in peripheral blood lead to the conclusion that the parasite does not affect hematopoiesis but interferes with some phase in the directed migration of leukocytes to specific sites.