Leishmania infantum Specific Humoral and Cellular Immune Responses in Cats and Dogs: A Comparative Cross-Sectional Study.

Dogs are the main reservoir of Leishmania infantum and display different immunological patterns correlating with the progression of infection to disease. Data about feline L. infantum adaptive immune response are scant. This study aimed to compare the prevalence and immune response in cats and dogs from the same endemic area of canine leishmaniosis. Stray cats (109) and rescued dogs (59) from Córdoba (Spain) were enrolled. Data about their exposure to L. infantum were analyzed by detection of parasite DNA, measurements of Leishmania-specific interferon-γ (whole blood assay in 57 cats and 29 dogs), and antibodies (enzyme-linked immunosorbent assay and immunofluorescence antibody test). An overall L. infantum prevalence of 30.5% in dogs and 30% in cats were found according to serology and PCR tests. Prevalence was 44.8% in dogs and 35.1% in cats tested also for interferon-γ production. Dogs showed higher anti-L. infantum antibody levels compared to cats. More than one-third of cats had contact with or were infected by L. infantum and they may contribute to the endemicity of leishmaniosis in the investigated region. The immunopathogenesis of feline L. infantum infection has similarities with dogs but cats show a lower level of adaptive immune response compared to dogs.

Association between feline immunodeficiency virus and Leishmania infantum infections in cats: a retrospective matched case-control study.

BACKGROUND: Feline leishmaniosis caused by Leishmania infantum is often associated with feline immunodeficiency virus (FIV) infection; however, the role and clinical significance of this coinfection remain unknown. This study aimed to assess whether FIV is associated with L. infantum infection in cats from canine leishmaniosis endemic areas and to report the clinical signs and hematological alterations associated with coinfection. METHODS: A retrospective matched case-control study (ratio 1:2) was conducted. Data of clinical examination and complete blood count (CBC) were selected from a cohort of 705 cats examined for epidemiological studies on feline leishmaniosis conducted between 2012 and 2019. Ninety-one FIV seropositive cases and 182 FIV seronegative control cats were selected. Matching was done according to age, sex, lifestyle and geographic provenience of case cats. Rapid ELISA devices were mainly used to detect anti-FIV antibodies. Anti-Leishmania IgG antibodies were detected by indirect-immunofluorescence test (IFAT). Leishmania DNA was searched in blood, oral and conjunctival swabs by quantitative real-time PCR. RESULTS: Feline immunodeficiency virus seropositive cats had no hematological abnormalities suggestive of an advanced stage of FIV infection and were statistically more frequently IFAT positive, and their risk of being L. infantum antibody positive was 2.8 greater than in the FIV seronegatives. The association of FIV seropositivity with L. infantum antibody positivity was confirmed in the univariable model of logistic regression. A multivariate model found FIV infection and L. infantum PCR positivity as predictors of a positive L. infantum IFAT result. Male outdoor cats from rural or suburban areas were at risk for FIV and L. infantum antibody positivity. Clinical signs more frequently associated with the coinfection were oral lesions, pale mucous membranes and low body condition score (BCS). CONCLUSIONS: This study documents that FIV seropositive cats with no hematological abnormalities suggestive of an advanced stage of FIV infection are more prone to be L. infantum seroreactive by IFAT in endemic areas. Therefore, FIV seropositive cats should be tested for L. infantum antibodies and treated for preventing sand fly bites. Pale mucous membranes, low BCS and oral lesions but no CBC abnormalities were significantly associated with the coinfection.

Identification of the Vasoconstriction-Inhibiting Factor (VIF), a Potent Endogenous Cofactor of Angiotensin II Acting on the Angiotensin II Type 2 Receptor.

BACKGROUND: The renin-angiotensin system and especially the angiotensin peptides play a central role in blood pressure regulation. Here, we hypothesize that an as-yet unknown peptide is involved in the action of angiotensin II modulating the vasoregulatory effects as a cofactor. METHODS AND RESULTS: The peptide with vasodilatory properties was isolated from adrenal glands chromatographically. The effects of this peptide were evaluated in vitro and in vivo, and the receptor affinity was analyzed. The plasma concentration in humans was quantified in patients with chronic kidney disease, patients with heart failure, and healthy control subjects. The amino acid sequence of the peptide from bovine adrenal glands was HSSYEDELSEVL EKPNDQAE PKEVTEEVSSKDAAE, which is a degradation product of chromogranin A. The sequence of the peptide isolated from human plasma was HSGFEDELSEVLENQSSQAELKEAVEEPSSKDVME. Both peptides diminished significantly the vasoconstrictive effect of angiotensin II in vitro. Therefore, we named the peptide vasoconstriction-inhibiting factor (VIF). The vasoregulatory effects of VIF are mediated by the angiotensin II type 2 receptor. VIF impairs angiotensin II-induced phosphorylation of the p38 mitogen-activated protein kinase pathway but not of extracellular-regulated kinase 1/2. The vasodilatory effects were confirmed in vivo. The plasma concentration was significantly increased in renal patients and patients with heart failure. CONCLUSIONS: VIF is a vasoregulatory peptide that modulates the vasoconstrictive effects of angiotensin II by acting on the angiotensin II type 2 receptor. It is likely that the increase in VIF may serve as a counterregulatory effect to defend against hypertension. The identification of this target may help us to understand the pathophysiology of renal and heart failure and may form a basis for the development of new strategies for the prevention and treatment of cardiovascular disease.