Chronic demodicosis in patients with immune dysregulation: An unexpected infectious manifestation of Signal transducer and activator of transcription (STAT)1 gain-of-function.

Signal transducer and activator of transcription (STAT)1 heterozygous gain-of-function (GOF) mutations are known to induce immune dysregulation and chronic mucocutaneous candidiasis (CMCC). Previous reports suggest an association between demodicosis and STAT1 GOF. However, immune characterization of these patients is lacking. Here, we present a retrospective analysis of patients with immune dysregulation and STAT1 GOF who presented with facial and ocular demodicosis. In-depth immune phenotyping and functional studies were used to characterize the patients. We identified five patients (three males) from two non-consanguineous Jewish families. The mean age at presentation was 11.11 (range = 0.58-24) years. Clinical presentation included CMCC, chronic demodicosis and immune dysregulation in all patients. Whole-exome and Sanger sequencing revealed a novel heterozygous c.1386C>A; p.S462R STAT1 GOF mutation in four of the five patients. Immunophenotyping demonstrated increased phosphorylated signal transducer and activator of transcription in response to interferon-α stimuli in all patients. The patients also exhibited decreased T cell proliferation capacity and low counts of interleukin-17-producing T cells, as well as low forkhead box protein 3+ regulatory T cells. Specific antibody deficiency was noted in one patient. Treatment for demodicosis included topical ivermectin and metronidazole. Demodicosis may indicate an underlying primary immune deficiency and can be found in patients with STAT1 GOF. Thus, the management of patients with chronic demodicosis should include an immunogenetic evaluation.

Quantitative proteomic profiling of immune responses to Ichthyophthirius multifiliis in common carp skin mucus.

Ichthyophthirius multifiliis, a ciliated protozoan parasite, causes ichthyophthiriasis and leads to considerable economic losses to the aquaculture industry. Understanding the fish immune response and host-parasite interactions could support developing novel strategies for better disease management and control. Fish skin mucus is the first line of defence against infections through the epidermis. Yet, the common carp, Cyprinus carpio, protein-based defence strategies against infection with I. multifiliis at this barrier remain elusive. The skin mucus proteome of common carp was investigated at 1 day and 9 days post-exposure with I. multifiliis. Using nano-LC ESI MS/MS and statistical analysis, the abundance of 19 immune related and signal transduction proteins was found to be differentially regulated in skin mucus of common carp in response to I. multifiliis. The analysis revealed increased abundance values of epithelial chloride channel protein, galactose-specific lectin nattection, high choriolytic enzyme 1 (nephrosin), lysozyme C, granulin and protein-glutamine gamma-glutamyltransferase 2 in I. multifiliis-exposed carp skin mucus. Multiple lectins and a diverse array of distinct serpins with protease inhibitor activity were identified likely implicated in lectin pathway activation and regulation of proteolysis, indicating that these proteins contribute to the carp innate immune system and the protective properties of skin mucus. The results obtained from this proteomic analysis enables a better understanding of fish host response to parasitic infection and gives insights into the key role skin mucus plays in protecting fish against deleterious effects of I. multifiliis.

Demodex canis regulates cholinergic system mediated immunosuppressive pathways in canine demodicosis.

Demodex canis infestation in dogs remains one of the main challenges in veterinary dermatology. The exact pathogenesis of canine demodicosis is unknown but an aberration in immune status is considered very significant. No studies have underpinned the nexus between induction of demodicosis and neural immunosuppressive pathways so far. We have evaluated the involvement of cholinergic pathways in association with cytokines regulation as an insight into the immuno-pathogenesis of canine demodicosis in the present study. Remarkable elevations in circulatory immunosuppressive cytokine interleukin-10 and cholinesterase activity were observed in dogs with demodicosis. Simultaneously, remarkable reduction in circulatory pro-inflammatory cytokine tumour necrosis factor-alpha level was observed in dogs with demodicosis. Findings of the present study evidently suggest that Demodex mites might be affecting the cholinergic pathways to induce immunosuppression in their host and then proliferate incessantly in skin microenvironment to cause demodicosis.

Avian schistosomes and outbreaks of cercarial dermatitis.

Cercarial dermatitis (swimmer's itch) is a condition caused by infective larvae (cercariae) of a species-rich group of mammalian and avian schistosomes. Over the last decade, it has been reported in areas that previously had few or no cases of dermatitis and is thus considered an emerging disease. It is obvious that avian schistosomes are responsible for the majority of reported dermatitis outbreaks around the world, and thus they are the primary focus of this review. Although they infect humans, they do not mature and usually die in the skin. Experimental infections of avian schistosomes in mice show that in previously exposed hosts, there is a strong skin immune reaction that kills the schistosome. However, penetration of larvae into naive mice can result in temporary migration from the skin. This is of particular interest because the worms are able to migrate to different organs, for example, the lungs in the case of visceral schistosomes and the central nervous system in the case of nasal schistosomes. The risk of such migration and accompanying disorders needs to be clarified for humans and animals of interest (e.g., dogs). Herein we compiled the most comprehensive review of the diversity, immunology, and epidemiology of avian schistosomes causing cercarial dermatitis.

Cutaneous acquired toxoplasmosis in a child: a case report and review of the literature.

Cutaneous toxoplasmosis is a rare and diagnostically challenging entity. Today, the acquired form occurs predominantly in immunocompromised patients with human immunodeficiency virus or after hematopoietic stem cell transplantation. We report a case of cutaneous toxoplasmosis in a 6-year-old girl after allogeneic stem cell transplantation for immune-mediated encephalopathy, first manifesting at 16 months of age. In the post-transplant setting, she developed a rash consisting of approximately 8 scattered 3­4-mm round, erythematous macules and papules on her back, abdomen, and right shoulder. Sections from a biopsy of a lesion on the back revealed numerous spherules tightly packed within small cystic structures in the epidermis. The diagnosis of cutaneous toxoplasmosis was confirmed by an immunohistochemical stain for Toxoplasma gondii and polymerase chain reaction on the peripheral blood for the T. gondii genome. This case should raise awareness that acquired toxoplasmosis with cutaneous involvement can occur in the pediatric population, particularly in immunocompromised patients after stem cell transplantation. Early diagnosis and treatment of this life-threatening opportunistic infection may improve patient outcomes.

Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.

Infection of the mammalian host by schistosome larvae occurs via the skin, although nothing is known about the development of immune responses to multiple exposures of schistosome larvae, and/or their excretory/secretory (E/S) products. Here, we show that multiple (4x) exposures, prior to the onset of egg laying by adult worms, modulate the skin immune response and induce CD4(+) cell hypo-responsiveness in the draining lymph node, and even modulate the formation of hepatic egg-induced granulomas. Compared to mice exposed to a single infection (1x), dermal cells from multiply infected mice (4x), were less able to support lymph node cell proliferation. Analysis of dermal cells showed that the most abundant in 4x mice were eosinophils (F4/80(+)MHC-II(-)), but they did not impact the ability of antigen presenting cells (APC) to support lymphocyte proliferation to parasite antigen in vitro. However, two other cell populations from the dermal site of infection appear to have a critical role. The first comprises arginase-1(+), Ym-1(+) alternatively activated macrophage-like cells, and the second are functionally compromised MHC-II(hi) cells. Through the administration of exogenous IL-12 to multiply infected mice, we show that these suppressive myeloid cell phenotypes form as a consequence of events in the skin, most notably an enrichment of IL-4 and IL-13, likely resulting from an influx of RELMα-expressing eosinophils. We further illustrate that the development of these suppressive dermal cells is dependent upon IL-4Rα signalling. The development of immune hypo-responsiveness to schistosome larvae and their effect on the subsequent response to the immunopathogenic egg is important in appreciating how immune responses to helminth infections are modulated by repeated exposure to the infective early stages of development.

Cutaneous gnathostomiasis with recurrent migratory nodule and persistent eosinophilia: a case report from China.

The present study reports a human case of cutaneous gnathostomiasis with recurrent migratory nodule and persistent eosinophilia in China. A 52-year-old woman from Henan Province, central China, presented with recurrent migratory reddish swelling and subcutaneous nodule in the left upper arm and on the back for 3 months. Blood examination showed eosinophila (21.2%), and anti-sparganum antibodies were positive. Skin biopsy of the lesion and histopathological examinations revealed dermal infiltrates of eosinophils but did not show any parasites. Thus, the patient was first diagnosed as sparganosis; however, new migratory swellings occurred after treatment with praziquantel for 3 days. On further inquiring, she recalled having eaten undercooked eels and specific antibodies to the larvae of Gnathostoma spinigerum were detected. The patient was definitely diagnosed as cutaneous gnathostomiasis caused by Gnathostoma sp. and treated with albendazole (1,000 mg/day) for 15 days, and the subsequent papule and blister developed after the treatment. After 1 month, laboratory findings indicated a reduced eosinophil count (3.3%). At her final follow-up 18 months later, the patient had no further symptoms and anti-Gnathostoma antibodies became negative. Conclusively, the present study is the first report on a human case of cutaneous gnathostomiasis in Henan Province, China, based on the past history (eating undercooked eels), clinical manifestations (migratory subcutaneous nodule and persistent eosinophilia), and a serological finding (positive for specific anti-Gnathostoma antibodies).

Early skin immunological disturbance after Plasmodium-infected mosquito bites.

Although the role of regulatory T cells (Tregs) during malaria infection has been studied extensively, such studies have focused exclusively on the role of Treg during the blood stage of infection; little is known about the detailed mechanisms of Tregs and sporozoite deposition in the dermis by mosquito bites. In this paper we show that sporozoites introduced into the skin by mosquito bites increase the mobility of skin Tregs and dendritic cells (DCs). We also show differences in MHC class II and/or CD86 expression on skin-resident dendritic cell subtypes and macrophages. From the observed decrease of the number of APCs into draining lymph nodes, suppression of CD28 expression in conventional CD4 T cells, and a low homeostatic proliferation of skin-migrated CD4 T found in nude mice indicate that Tregs may play a fundamental role during the initial phase of malaria parasite inoculation into the mammalian host.

Quantification of Demodex folliculorum by PCR in rosacea and its relationship to skin innate immune activation.

The aim of this study is to quantify D. folliculorum colonisation in rosacea subtypes and age-matched controls and to determine the relationship between D. folliculorum load, rosacea subtype and skin innate immune system activation markers. We set up a multicentre, cross-sectional, prospective study in which 98 adults were included: 50 with facial rosacea, including 18 with erythematotelangiectatic rosacea (ETR), and 32 with papulopustular rosacea (PPR) and 48 age- and sex-matched healthy volunteers. Non-invasive facial samples were taken to quantify D. folliculorum infestation by quantitative PCR and evaluate inflammatory and immune markers. Analysis of the skin samples show that D. folliculorum was detected more frequently in rosacea patients than age-matched controls (96% vs 74%, P < 0.01). D. folliculorum density was 5.7 times higher in rosacea patients than in healthy volunteers. Skin sample analysis showed a higher expression of genes encoding pro-inflammatory cytokines (Il-8, Il-1b, TNF-a) and inflammasome-related genes (NALP-3 and CASP-1) in rosacea, especially PPR. Overexpression of LL-37 and VEGF, as well as CD45RO, MPO and CD163, was observed, indicating broad immune system activation in patients with rosacea. In conclusion, D. folliculorum density is highly increased in patients with rosacea, irrespective of rosacea subtype. There appears to be an inverse relationship between D. folliculorum density and inflammation markers in the skin of rosacea patients, with clear differences between rosacea subtypes.

The role of keratinocytes in defense against infection.

PURPOSE OF REVIEW: The discovery of increasing numbers of epithelial antimicrobial peptides (AMPs), cytokines that specifically induce AMPs in epithelial cells, and mechanisms of its regulation point toward a central role of the keratinocyte as effector cell of the epithelial innate defense system. This review summarizes recent progress in understanding the keratinocyte's role in combating infection that can help to understand why skin is usually covered with microbes but normally not infected. RECENT FINDINGS: The AMP LL-37 has been identified as regulator of keratinocyte apoptosis. The hypothesis of a direct defense function of keratinocytes, combating bacterial, fungal, virus and parasite infection, is strengthened. The discovery of an IL-22-producing T-lymphocyte subpopulation implicates a role in AMP induction of keratinocytes. Multiple studies are adding to our understanding of how skin keratinocytes are interacting in skin barrier defects and with the microflora. Although in atopic patients AMP production is not generally impaired, in hyperIgE syndrome a lack of Th17 cytokines causes local Staphylococcus aureus infection due to a defective keratinocyte defense system. Ultraviolet radiation induces AMPs and thus may have beneficial effects to combat skin infection. SUMMARY: There is better understanding of the keratinocyte's role in the skin's innate defense system, and these data can help to generate therapeutics that can activate this defense system.

Determination of CD4+ and CD8+ T cells in the peripheral blood of dogs with demodicosis.

The aim of this study was to evaluate the CD4+/CD8+ ratio in peripheral blood of dogs with localized and generalized demodicosis. Sixteen dogs were examined, 8 with localized and 8 with generalized demodicosis, while 8 healthy dogs were used as controls. Peripheral blood was obtained and CD4+ and CD8+ T cells were determined by flow cytometry. Significantly higher numbers of CD8+ T cells and lower numbers of CD4+ T cells were found in dogs with generalized demodicosis compared to dogs with localized demodicosis and healthy controls. Significantly higher numbers of CD8+ T cells and lower numbers of CD4+ T cells were also found in dogs with localized demodicosis compared to healthy controls. The CD4+/CD8+ ratio was also found to be significantly lower in dogs with generalized demodicosis in comparison with dogs with localized demodicosis and healthy controls. It is concluded that significant alteration in the CD4+/CD8+ ratio may be implicated in the pathogenesis of generalized canine demodicosis.

Quantification of immuno-regulatory cytokine and toll-like receptors gene expression in dogs with generalized demodicosis.

The proliferation of Demodex mites is mainly controlled by host immunity; however, the precised mechanism of host-mite interplay and host immune response in the cutaneous microenvironment of dogs with generalized demodicosis (GD) are not yet established. In the present study, we envisaged the alterations in the expression of toll-like receptors (TLRs) and immuno-regulatory cytokine gene in the skin lesions and peripheral blood mononuclear cells (PBMCs) of dogs with GD. The expression of TLR2, TLR6, IFN-γ, TGF-ß and IL-10 genes in the skin lesions and PBMCs of 15 dogs with GD was quantified by qRT-PCR. Compared to healthy dogs, significantly elevated expression of TLR2 (P = 0.048), TGF-ß (P = 0.04) and IL-10 (P = 0.012) were found in the PBMCs of dogs with GD. Conversely, there was significantly reduced expression of TLR6 gene (P = 0.021) in the PBMCs of these dogs. The infested dogs also revealed significantly elevated expression of TLR2 gene (P = 0.034) in the skin lesions, while, the expression of the TLR6 gene was found to be significantly (P = 0.004) reduced. Interestingly, significant alterations in TGF-ß (P = 0.105) and IL-10 (P = 0.162) genes expression were not observed in the skin lesions of diseased dogs. Our findings suggest that Demodex mites contribute to a different systemic and cutaneous immune response in dogs for their proliferation, and consequently the development of GD. Therefore, Demodex mites might be inducing the immunosuppression through activating the systemic over-expression of immunosuppressive cytokines; however, in the cutaneous lesions, the expression of immunosuppressive cytokines remained unaltered. Both systemic and local over-expression of TLR2 and reduced expression of TLR6 genes might be responsible for the inflammatory signs of canine demodicosis and helping to the mite to escape the host immunity.

Cutaneous cytokine gene expression and cellular responses in lambs infested with the louse, Bovicola ovis, and following intradermal injection of crude louse antigen.

The present study was undertaken to investigate further the immunological responses in the skin of lambs to natural louse infestation and following intradermal allergen challenge. Bovicola ovis-infested (n=7) and naïve (n=7) Romney lambs received four intradermal injections each of crude louse Ag and diluent control solutions on the dorso-lateral chest. From each lamb, skin samples were obtained from untreated skin and, at 4, 24, 48 and 72 h following injection, from one each of the Ag- and diluent-injected skin sites. Levels of acetylcholinesterase-positive Langerhans and MHC II(+) cells in the epidermis as well as MHC II(+), CD1b(+), T19(+) and IgE(+) cells, eosinophils, and diffuse IgE staining in the dermis were significantly elevated in infested compared to naïve lambs (all p< or =0.01). Additionally, gene expression of interleukin-4 (IL-4), IL-5, IL-13 (all p< or =0.001) and IL-10 (p< or =0.05) was significantly higher in the skin of infested compared to naïve lambs while TNF-alpha and IFN-gamma gene expression were not significantly different between the two groups. Intradermal injection of louse Ag led to immediate and late phase responses in the infested lambs while the naïve lambs showed only minimal responses. Levels of dermal MHC II(+), CD1b(+), T19(+)and IgE(+) cells, eosinophils and diffuse IgE staining in infested lambs following injection of louse Ag were similar to or exceeded those in untreated skin and, with few exceptions, were higher than in naïve lambs. Additionally, cytokine gene expression of IL-4, IL-5, IL-13 and IL-10 increased to peak levels 4 h following Ag injection in the infested lambs (p< or =0.001, < or =0.05, < or =0.05 and < or =0.001 respectively compared to untreated controls) and remained significantly elevated compared to that observed in the naïve controls for the duration of the experiment. Significant elevations of MHC II(+) cells and IL-4, IL-5, IL-13 and IL-10 gene expression were observed in the louse-naïve lambs following injection of louse Ag but were much less pronounced than in the infested lambs. These results indicated that louse infestation in lambs elicited a highly skewed Th2 immuno-inflammatory response with many characteristics similar to those seen with other parasitic infections and also in atopic dermatitis.

Improved general health of international adoptees, but immunization status still insufficient.

We studied the demographic and clinical data from 495 adopted children seen between January 2002 and January 2007 to evaluate the medical condition and immunization status of international adoptees. The data of children from Chinese origin (53.5%) were compared to children arriving from other countries. Medical problems requiring treatment were present in 42.8% of the children. Parasitic gastrointestinal infection (22.0%) and skin abnormalities (22.4%) were diagnosed most often. Hepatitis B (1.2%) and tuberculosis (1%) were documented in some children; HIV, hepatitis C, and syphilis were not seen in any of the children. Antibody levels against diphtheria and tetanus were insufficient in about half of all children, particularly in those from China. In conclusion, most adoptive children had a good general health, with only a few having major medical problems. Many adoptive children had an inadequate immunization status.

Tetrahymena sp. infection in guppies, Poecilia reticulata Peters: parasite characterization and pathology of infected fish.

Tetrahymena sp. infection was diagnosed in guppies imported from Singapore. The parasite was isolated (Tet-NI) and optimally cultured in vitro in RM-9 medium. Cytological analyses [silver-staining and scanning electron microscopy (SEM)] revealed a pyriform-shaped, 64 x 41-microm holotrich ciliate without caudal cilium, containing a macro-nucleus (18.25 x 16.83 microm) and micro-nucleus (5.73 x 5.40 microm). Wet-mount examination and histological analyses of fish exposed to the parasite by co-habitation, immersion and infection by i.p. (intra-peritoneal) and i.m. (intra-muscular) injection revealed numerous ciliates on the skin, and in the gill and caudal fin blood vessels. Ciliates surrounded internal organs, the peri-orbital region of the eye, and were observed inside developing guppy embryos. Some muscle necrosis was associated with infection, but little or no inflammatory response. Immersion, co-habitation and i.m. injection caused relatively high infection rates and levels in the skin and tail, and lower infection in the gill blood vessels and internal organs; i.p. injection caused higher infection in the gill blood vessels and internal organs. Co-habited fish had relatively high infection levels in the hind-gut sub-mucosa. This is the first report of controlled systemic infection by Tetrahymena sp.

Toll-like receptors 2, 4 and 7, interferon-gamma and interleukin 10, and programmed death ligand 1 transcripts in skin from dogs of different clinical stages of leishmaniosis.

BACKGROUND: Canine leishmaniosis (CanL) caused by Leishmania infantum can have several dermatological manifestations. The type of immune response elicited against the parasite appears to be at the basis for such clinical variability. Much of the work in CanL has focused on adaptive immune response and there are scarce data on the importance of the innate immune responses. Moreover, few studies have evaluated the immunological response in the cutaneous lesions in dogs naturally infected with L. infantum and with different degrees of disease severity, and no study has compared clinically-lesioned with normal-looking skin. METHODS: We determined and compared the transcription of toll like receptors (TLRs) 2, 4 and 7, interferon gamma (IFN-γ), interleukin (IL) 10 and programmed cell death protein ligand (PD-L) 1 by real-time PCR in paired clinically-lesioned and normal-looking skin from 25 diseased dogs (mild disease-stage I (n = 11) and moderate to severe disease-stages II and III (n = 14) as well as in normal-looking skin from healthy dogs (n = 10) from a non-endemic area. We also assessed the association between the transcripts in clinically-lesioned and normal-looking skin of dogs with leishmaniosis with clinicopathological, immunological and parasitological findings. RESULTS: Clinically-lesioned skin from mildly affected dogs was characterized by a significant upregulation of TLR2 (P < 0.0001) and IL-10 (P = 0.021) and downregulation of TLR7 (P = 0.004) when compared with more severely affected dogs. Normal-looking skin of mildly affected dogs was characterized by a significant lower expression of TLR7 (P = 0.003), IFN-γ (P < 0.0001) and PD-L1 (P = 0.001) when compared with more severely affected dogs. TLR2, TLR4, IL-10 and IFN-γ upregulation in clinically-lesioned skin was correlated with lower disease severity while TLR7 upregulation was correlated with markers of disease severity. Upregulation of TLR7, IL-10, IFN-γ and PD-L1 in normal-looking skin was correlated with disease severity. CONCLUSIONS: This study demonstrated different expression profiles of immune genes in clinically-lesioned and normal-looking skin among mildly and more severely affected dogs. These immunological conditions might favor the maintenance and replication of the parasite in the skin of more severely affected dogs.

Wolbachia in Dirofilaria repens, an agent causing human subcutaneous dirofilariasis.

Human subcutaneous dirofilariasis is an increasingly reported zoonosis caused by several filarial species, in particular by Dirofilaria (Nochtiella) repens. Like many filarial worms, D. repens harbors the bacterial endosymbiont Wolbachia that has been implicated in the inflammatory features of filarial infection. Immunohistochemical staining against the Wolbachia surface protein (WSP) was carried out on 14 skin nodules and showed numerous bacteria within the intact worms and occasional positive staining within the surrounding inflammatory infiltrate. Serum samples from 11 of these patients resulted positive for total immunoglobulin G titers against WSP as examined in enzyme-linked immunosorbent assay. This is the first description of Wolbachia distribution in D. repens and the first report of specific immune response to Wolbachia in patients with subcutaneous dirofilariasis.

Larva currens in a patient scheduled for renal transplant.

We present a case of larva currens in a patient scheduled for renal transplant. Larva currens is an eruption caused by Strongyloides stercoralis, characterized most often by a pathognomonic, migratory, rapidly extending, serpiginous, urticarial eruption. Infected patients who are immunocompromised are at risk for disseminated and often fatal infection. In disseminated disease, diffuse petechiae and purpura may be present, and periumbilical ecchymoses may resemble thumbprints. The dermatologist may be in a unique position to diagnose this condition and institute therapy. Although found endemically in the United States, the increasingly international nature of medical practice and transplantation medicine causes an increase in the number of patients who may present for evaluation.

Stimulation of the in vitro migration of ovine eosinophils by factors derived from the sheep scab mite, Psoroptes ovis.

The ectoparasitic astigmatid mite Psoroptes ovis causes sheep scab, a highly contagious, severe allergic dermatitis associated with damage to the fleece and hide, loss of condition and occasional mortality. The scab lesion is characterized by a massive infiltration of eosinophils that begins very rapidly after infection. This paper reports the finding that mite-derived factors directly enhance the migration of ovine eosinophils in vitro. Significant (p < 0.01) and dose-dependent (r = 0.972 +/- 0.018 (SD)) activity was initially identified in whole mite extracts, by comparison with medium controls in an assay based on modified Boyden chambers and ovine bone marrow target cells. Similar pro-migratory activity (p < 0.005; r = 0.928 +/- 0.069 (SD)) was detected in washes containing mite excretory/secretory material. By direct comparison with migration ratios (n = 3) for defined chemotactic (rmeotaxin = 3.430 +/- 0.360 (SD)) and chemokinetic (rminterleukin-5 = 0.982 +/- 0.112 (SD)) stimuli it was determined that the activity in both mite extracts (0.992 +/- 0.038 (SD)) and mite washes (0.969 +/- 0.071 (SD)) was chemokinetic. Subsequent experiments (n = 3) in which live mites were incorporated directly into the in vitro assay system indicated that they produced factors that significantly (p < 0.001) enhanced eosinophil migration to a degree directly related to mite numbers (r = 0.993 +/- 0.005 (SD)). The identity of the factor(s) responsible is uncertain, but their presence suggests that mites may be capable of directly activating eosinophils in vivo, and raises the possibility that mites could directly influence, perhaps even initiate, the rapid early tissue eosinophilic response observed in experimental sheep scab infections.