Insights on adaptive and innate immunity in canine leishmaniosis.

Canine leishmaniosis (CanL) is caused by the parasite Leishmania infantum and is a systemic disease, which can present with variable clinical signs, and clinicopathological abnormalities. Clinical manifestations can range from subclinical infection to very severe systemic disease. Leishmaniosis is categorized as a neglected tropical disease and the complex immune responses associated with Leishmania species makes therapeutic treatments and vaccine development challenging for both dogs and humans. In this review, we summarize innate and adaptive immune responses associated with L. infantum infection in dogs, and we discuss the problems associated with the disease as well as potential solutions and the future direction of required research to help control the parasite.

Haematozoans from deep water fishes trawled off the Cape Verde Islands and over the Porcupine Seabight, with a revision of species within the genus Desseria (Adeleorina: Haemogregarinidae).

Archived blood smears from 32 of 113 fishes in 18 families and 12 orders, trawled from deep North Atlantic waters off the Cape Verde Islands in 1999 and over the Porcupine Seabight in 2001 were found to harbour haematozoans. These included four species of haemogregarines (Adeleorina, Haemogregarinidae) and a species of trypanosome (Trypanosomatina, Trypanosomatidae) located in Porcupine Seabight fishes. Also present were Haemohormidium-like structures of uncertain status found in samples from this location and from the Cape Verde Islands. Although material was limited, two of the haemogregarines were provisionally named Desseria harriottae sp. n. from Harriotta raleighana Goode et Bean (Chimaeriformes, Rhinochimaeridae), and Haemogregarina bathysauri sp. n. from Bathysaurus ferox Günther (Aulopiformes, Bathysauridae). The two remaining haemogregarines were identified as Desseria marshalllairdi (Khan, Threlfall et Whitty, 1992) from Halosauropsis macrochir (Günther) (Notacanthiformes, Halosauridae), and Haemogregarina michaeljohnstoni (Davies et Merrett, 2000) from Cataetyx laticeps Koefoed (Ophidiformes, Bythitidae). The name H. michaeljohnstoni was proposed to replace Haemogregarinajohnstoni Davies et Merrett, 2000 from C. laticeps and to avoid confusion with Hepatozoon johnstoni (Mackerras, 1961) Smith, 1996 from varanid lizards, originally named Haemogregarina johnstoni Mackerras, 1961. The trypanosome formed a mixed parasitaemia with D. harriottae in H. raleighana and was provisionally named Trypanosoma harriottae sp. n. No blood parasites had been described previously from cartilaginous fishes of the Holocephali, making the finds in H. raleighana unique. Haemohormidium-like structures were located in erythrocytes in one fish, Coryphaenoides armatus (Hector), among the Cape Verde Islands samples and in 12 species of fishes from the Porcupine Seabight; all these hosts were bony fishes. Finally, the haemogregarine species listed in the genus Desseria Siddall, 1995 were reassessed. Of the original list of 41 species, 30 were retained and 5 species added, including D. harriottae, so that the genus now contains 35 species.

Toxoplasma gondii detection in cattle: A slaughterhouse survey.

Toxoplasmosis is a zoonotic disease caused by the protozoan parasite Toxoplasma gondii. Ingestion of raw or undercooked meat containing viable cysts has been suggested to be a major source of T. gondii infection in humans. Suboptimal performance of serological assays in cattle has traditionally precluded accurate quantification of the extent to which cattle populations are infected and their meat harbour tissue cysts. In the absence of accurate estimates of the level of infection in the animal population, assessments of likely human exposure through the consumption of cattle meat remain highly speculative. Following the development of novel and sensitive molecular methods that can be applied to the relatively large numbers of samples required in observational studies, the first quantitative estimates of the frequency of T. gondii in meat samples from naturally infected cattle have become available recently. Such estimates are critical for the development of quantitative risk assessment models that could be used to inform food safety policies. The aim of this study was to generate the first estimates of the prevalence of T. gondii infection in a sample of cattle exposed to natural levels of infection and slaughtered for human consumption in the UK under commercial conditions. Such estimates provide great value to the global assessment of T. gondii burden given the scarcity of data available on the frequency of natural infection in cattle populations worldwide. Between October 2015 and January 2016 diaphragm samples were collected from 305 animals, slaughtered in ten commercial slaughterhouses across the UK. Movement histories showed that the animals sampled (41.6% females and 58.4% males) had passed through a total of 614 farms and 40 livestock markets across the country. Five animals (1.6%) were deemed positive for T. gondii following magnetic capture real-time PCR, confirmed by amplicon sequencing. The true prevalence of infection was estimated to be 1.79%. All positive animals were male, none of whom had been on the same farm and/or livestock market before slaughter and there was no apparent geographic pattern. The results from this study suggest a low level of infection in cattle raised and slaughtered in the UK and can be used to populate the first stages of formal risk assessments to quantify the likely extent of human exposure to T. gondii through the consumption of beef with relevance to the UK, EU and rest of the world.

Histopathological findings and detection of Toll-like receptor 2 in cutaneous lesions of canine leishmaniosis.

A broad spectrum of clinical manifestations ranging from a chronic subclinical infection to a non-self-limiting illness has been described for canine leishmaniosis (CanL). This clinical variation is determined by a variable immune response, presumably genetically determined, against the infection. Although different types of adaptive immune response in dogs with CanL have been investigated in several studies, the mechanisms that underlie and determine this variability are still poorly understood. It is currently thought that innate immune response, and particularly the role of specific mediators of the innate immune system, such as toll-like receptors (TLRs), plays a central role in this polarization. However, there is limited data available concerning the role that TLRs play in canine Leishmania infantum infection. The objective of this descriptive study was to characterize and compare the inflammatory pattern, the Leishmania burden and expression of TLR2 in skin lesions derived from dogs with different clinical stages of leishmaniosis and cutaneous lesions. Routine histology, Leishmania and TLR2 immunohistochemistry assays were performed in 11 patients with papular dermatitis (stage I - mild disease) and 10 patients with other cutaneous lesions (stage II-III - moderate to severe disease). A significantly higher frequency of granuloma formation was demonstrated in skin samples of dogs with stage I when compared with dogs of stage II-III. Although not statistically significant, a trend for a lower parasite burden was observed for skin lesions of dogs with stage I when compared with dogs of stage II-III. A lower expression of TLR2 in skin biopsies from dogs with stage I was statistically significant compared with stage II-III. The results obtained in this study indicated an association with TLR2 in the pathogenesis of canine cutaneous leishmaniosis. Further studies are required to fully elucidate these findings.

Transcription of Toll-Like Receptors 2, 3, 4 and 9, FoxP3 and Th17 Cytokines in a Susceptible Experimental Model of Canine Leishmania infantum Infection.

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model.