Pathogenesis of Anemia in Canine Babesiosis: Possible Contribution of Pro-Inflammatory Cytokines and Chemokines—A Review

Abstract

Canine babesiosis is a tick-borne protozoan disease caused by intraerythrocytic parasites of the genus Babesia. The infection may lead to anemia in infected dogs. However, anemia is not directly caused by the pathogen. The parasite’s developmental stages only have a marginal role in contributing to a decreased red blood cell (RBC) count. The main cause of anemia in affected dogs is the immune response to the infection. This response includes antibody production, erythrophagocytosis, oxidative damage of RBCs, complement activation, and antibody-dependent cellular cytotoxicity. Moreover, both infected and uninfected erythrocytes are retained in the spleen and sequestered in micro-vessels. All these actions are driven by pro-inflammatory cytokines and chemokines, especially IFN-γ, TNF-α, IL-6, and IL-8. Additionally, imbalance between the actions of pro- and anti-inflammatory cytokines plays a role in patho-mechanisms leading to anemia in canine babesiosis. This article is a review of the studies on the pathogenesis of anemia in canine babesiosis and related diseases, such as bovine or murine babesiosis and human or murine malaria, and the role of pro-inflammatory cytokines and chemokines in the mechanisms leading to anemia in infected dogs.

The effect of transfusion of erythrocyte mass on clinical and haematological indicators of dogs with hemolytic anaemia caused by babesiosis

“…No structural changes and concomitant pathologies that could affect the statistical reliability of the study results were recorded in the dogs selected for the study based on the results of ultrasound. The main contraindications to haemotransfusion for babesiosis, as noted by W. Zygner et al (2023) and R. Zaremba et al (2019), are severe liver and kidney dysfunction, which were not diagnosed in the studied animals. Before starting the therapy, the animals underwent biochemical and clinical blood tests (Tables 2, 3).…”

“…General intoxication of the body develops due to the accumulation of underoxidised decomposition products, which leads to a deterioration in the clinical condition of the animal. A decrease in haematocrit, according to the results of studies by W. Zygner et al (2023), is a prognostic marker in dogs infected with B. Canis, and it is significantly lower in non-survivors compared to survivors. Anaemia in canine babesiosis is caused by intravascular and extravascular haemolysis.…”

“…Otsuka et al (2002) showed that this ability is particularly pronounced in washed red blood cells. W. Zygner et al (2023) reported the absence or minimal content of decay products and vasoactive substances (potassium, sodium, nitrogen, serotonin, histamine) when using red blood cells. S.Y.…”

Canine Babesiosis Caused by Large Babesia Species: Global Prevalence and Risk Factors—A Review

“…Severe babesiosis, like human malaria and sepsis, is considered an immune-mediated disease which is characterized by cytokine storms and tissue hypoxia in various organs [ 12 , 13 , 14 , 15 ]. The disease may lead to anemia, coagulopathy, kidney injury, hepatopathy, pancreatitis, cardiac disorders, pulmonary edema, cerebral complications, endocrine disorders, systemic inflammatory response syndrome, multiple organ dysfunction syndrome, and septic shock in infected dogs [ 12 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. Infections caused by large Babesia species have been recognized in dogs on all continents, except Antarctica [ 1 ].…”

Immune Response of the Host and Vaccine Development

“…In many cases, the immune response contributes to the pathology that develops during the infection process, and this should also be considered during vaccine development. Here, Zygner et al [ 14 ] widely review the role of pro-inflammatory cytokines and chemokines in the development of anemia in dogs suffering from babesiosis. The authors describe several immune-related causes of anemia such as antibody production, erythrophagocytosis, oxidative damage of red blood cells, complement activation, and antibody-dependent cellular cytotoxicity, all of which are driven by pro-inflammatory cytokines and chemokines, especially IFN-γ, TNF-α, IL-6, and IL-8.…”