Veterinary allergy diagnosis: past, present and future perspectives

Fleas, several aeroallergens as well as many food allergens are the most common allergenic sources for animals and frequent cause of allergic reactions with different target organs such as skin, eyes, and respiratory or digestive systems. Allergy diagnosis needs to follow well-established guidelines under clinical and laboratory approaches. Since 1980 with the Hanifin & Rajka’s criteria for the diagnosis of atopic dermatitis (AD) in humans, successive proposals have been developed to identify atopic dermatitis in dogs. A consensual plan was first proposed by Willemse in 1986 undergoing several modifications in 1994. Prélaud and colleagues made important changes to the plan in 1998 and it was further adjusted by Favrot in 2009. In 2010, this plan was approved by the International Task Force on Canine Atopic Dermatitis (CAD). It was subjected in 2015 to minor updates with regard to therapeutic options. To improve diagnostic accuracy by integrating the basic knowledge on sensitization development and allergen nature and diversity, allergen sources and implicated molecular allergens for animals should be clearly identified. As well as in human medicine, this molecular epidemiology concept is essential for the veterinary allergy diagnosis in the near future, standing as the basis of a component-resolved diagnosis (CRD). Besides current pharma- cotherapy, it will be highly relevant to increase the efficiency of the avoidance measures and specific immunotherapy. Clinical guidelines will lead to at least 80 % of positive diagnosis of atopy, but newer laboratory methods in veterinary medicine aiming to a more precise diagnosis and a better integration of the clinical/laboratory diagnostic course are needed. Allergoms identification for animals, from different allergen sources proteoms should become a priority in veterinary allergology, in order to allow the intended CRD, which is essential to understand the cross-reaction phenomena, allowing a more precise and possibly effective component-resolved immunotherapy (CRIT). Further research has been carried out for a better understanding of the interaction between allergic clinical condition and immune pathophysiology. As well as in human medicine, a deeper knowledge of the molecular immunological mechanisms in veterinary allergy — with their specific allergen triggers — will also provide the veterinary allergist with the necessary information to act more efficiently in the future.

Exploratory spatial analysis of social and environmental factors associated with the incidence of Ross River Virus in Brisbane, Australia

We used geographic information systems and a spatial analysis approach to explore the pattern of Ross River virus (RRV) incidence in Brisbane, Australia. Climate, vegetation and socioeconomic data in 2001 were obtained from the Australian Bureau of Meteorology, the Brisbane City Council and the Australian Bureau of Statistics, respectively. Information on the RRV cases was obtained from the Queensland Department of Health. Spatial and multiple negative binomial regression models were used to identify the socioeconomic and environmental determinants of RRV transmission. The results show that RRV activity was primarily concentrated in the northeastern, northwestern, and southeastern regions in Brisbane. Multiple negative binomial regression models showed that the spatial pattern of RRV disease in Brisbane seemed to be determined by a combination of local ecologic, socioeconomic, and environmental factors.

Chlamydial infection and spatial ascension of the female genital tract : a novel hybrid cellular automata and continuum mathematical model

Sexually transmitted chlamydial infection initially establishes in the endocervix in females, but if the infection ascends the genital tract, significant disease, including infertility, can result. Many of the mechanisms associated with chlamydial infection kinetics and disease ascension are unknown. We attempt to elucidate some of these processes by developing a novel mathematical model, using a cellular automata–partial differential equation model. We matched our model outputs to experimental data of chlamydial infection of the guinea-pig cervix and carried out sensitivity analyses to determine the relative influence of model parameters. We found that the rate of recruitment and action of innate immune cells to clear extracellular chlamydial particles and the rate of passive movement of chlamydial particles are the dominant factors in determining the early course of infection, magnitude of the peak chlamydial time course and the time of the peak. The rate of passive movement was found to be the most important factor in determining whether infection would ascend to the upper genital tract. This study highlights the importance of early innate immunity in the control of chlamydial infection and the significance of motility-diffusive properties and the adaptive immune response in the magnitude of infection and in its ascension.

Persistent chlamydial infections : role in inflammation and challenges for vaccine development.

The development of chlamydial vaccines continues to be a major challenge for researchers. While acute infections are the main target of vaccine development groups, Chlamydia is well known for its ability to establish chronic or persistent infections in its host. To date, little effort has focussed specifically on the challenges of vaccines to successfully combat the chronic or persistent phase of the disease and yet this will be a necessary aspect of any fully successful chlamydial vaccine. This short review specifically examines the phenomenon of chlamydial persistence and the unique challenges that this brings to vaccine development.

Apoptosis is induced in Chlamydia trachomatis infected HEp-2 cells by the addition of a combination innate immune activation compounds and the inhibitor wedelolactone

Problem: Innate immune activation of human cells, for some intracellular pathogens, is advantageous for vacuole morphology and pathogenic viability. It is unknown whether innate immune activation is advantageous to Chlamydia trachomatis viability. ----- ----- Method of study: Innate immune activation of HEp-2 cells during Chlamydia infection was conducted using lipopolysaccharide (LPS), polyI:C, and wedelolactone (innate immune inhibitor) to investigate the impact of these conditions on viability of Chlamydia. ----- ----- Results: The addition of LPS and polyI:C to stimulate activation of the two distinct innate immune pathways (nuclear factor kappa beta and interferon regulatory factor) had no impact on the viability of Chlamydia. However, when compounds targeting either pathway were added in combination with the specific innate immune inhibitor (wedelolactone) a major impact on Chlamydia viability was observed. This impact was found to be due to the induction of apoptosis of the HEp-2 cells under these conditions. ----- ----- Conclusion: This is the first time that induction of apoptosis has been reported in C. trachomatis-infected cells when treated with a combination of innate immune activators and wedelolactone.

Chlamydial infection of immune cells : altered function and implications for disease

Chlamydia trachomatis is an obligate intracellular bacterial pathogen that infects the genital and ocular mucosa of humans, causing infections that can lead to pelvic inflammatory disease, infertility, and blinding trachoma. C. pneumoniae is a respiratory pathogen that is the cause of 12–15% of community-acquired pneumonia. Both chlamydial species were believed to be restricted to the epithelia of the genital, ocular, and respiratory mucosa; however, increasing evidence suggests that both these pathogens can be isolated from peripheral blood of both healthy individuals and patients with inflammatory conditions such as coronary artery disease and asthma. Chlamydia can also be isolated from brain tissues of patients with degenerative neurological disorders such as Alzheimer’s disease and multiple sclerosis, and also from certain lymphomas. An increasing number of in vitro studies suggest that some chlamydial species can infect immune cells, at least at low levels. These infections may alter immune cell function in a way that promotes chlamydial persistence in the host and contributes to the progression of several chronic inflammatory diseases. In this paper, we review the evidence for the growth of Chlamydia in immune cells, particularly monocytes/macrophages and dendritic cells, and describe how infection may affect the function of these cells.

Transport of IgG across the blood-luminal barrier of the male reproductive tract of the rat and the effect of estradiol administration on reabsorption of fluid and IgG by the epididymal ducts

In rats immunized systemically with tetanus toxoid the concentration of specific anti-tetanus-toxoid-specific IgG in fluid from the rete testis and cauda epididymidis were respectively 0.6% and 1.4% the concentration in blood serum. The extratesticular duct system reabsorbed 97% of the IgG and 99% of the fluid leaving the rete, but estradiol administration affected the site of reabsorption. In untreated rats, the ductuli efferentes reabsorbed 94% of the IgG and 96% of the fluid leaving the rete, whereas estradiol-treated rats reabsorbed 83% of the IgG and 86% of the fluid, and the ductus epididymidis fully compensated for these different effects of estradiol on the ductuli efferentes. The concentrations of IgG in secretions of the seminal vesicles and prostate gland were lower (0.1% and 0.3% respectively of the titers in blood serum) than in fluids from the extratesticular ducts, and were not affected by the administration of estradiol. RT-PCR showed that Fcgrt (neonatal Fc receptor, also known as FcRn) is expressed in the reproductive ducts, where IgG is probably transported across epithelium, being particularly strong in the ductuli efferentes (where most IgG was reabsorbed) and distal caput epididymidis. It is concluded that IgG enters the rete testis and is concentrated only 2.5-fold along the extratesticular duct system, unlike spermatozoa, which are concentrated 95-fold. Further, the ductus epididymidis can recognize and compensate for changes in function of the ductuli efferentes.

Syntaxin 11 binds Vti1b and regulates late endosome to lysosome fusion in macrophages

Syntaxin 11 (Stx11) is a SNARE protein enriched in cells of the immune system. Loss or mutation of Stx11 results in familial hemophagocytic lymphohistiocytosis type-4 (FHL-4), an autosomal recessive disorder of immune dysregulation characterized by high levels of inflammatory cytokines along with defects in T-cell and natural killer cell function. We show here Stx11 is located on endosomalmembranes including late endosomes and lysosomes in macrophages. While Stx11 did not form a typical trans-SNARE complex, it did bind to the Q-SNARE Vti1b and was able to regulate the availability of Vti1b to form the Q-SNARE complexes Stx6/Stx7/Vtib and Stx7/Stx8/Vti1b. The mutant form of Stx11 sequestered Vti1b from forming the Q-SNARE complex that mediates late endosome to lysosome fusion. Depletion of Stx11 in activated macrophages leads to an accumulation of enlarged late endocytic compartments, increased trafficking to the cell surface and inhibition of late endosome to lysosome fusion. These phenotypes arerescued by the expression of an siRNA-resistant Stx11 construct in Stx11-depleted cells. Our results suggest that by regulating the availability of Vti1b, Stx11 regulates trafficking steps between late endosomes, lysosomes and the cell surface in macrophages.