Cytauxzoonosis is a fatal disease of domestic cats in the Midwestern, mid-Atlantic, southeastern, and south-central United States caused by Cytauxzoon felis, a tick-borne parasite in the order Piroplasmida, family Theileriidae.1,2 Infected ticks transmit C felis during feeding, which is followed by schizogony of the parasite in monocytes throughout the body.3 Although C felis infection can be subclinical, clinical signs in infected cats include anorexia, signs of depression, lethargy, dehydration, pyrexia, dyspnea, icterus, and dark urine as well as the less common clinical signs of pallor, anemiainduced heart murmur, and increased capillary refill time. Hematologic findings may include normocytic, normochromic, nonregenerative anemia with pancytopenia or moderate neutrophilia.2,4
Since the discovery and description of C felis infections in the 1970s, little has been published regarding the immune response of cats to this disease. Investigators in 1 report5 described the formation of antibodies against the nonpathogenic, erythrocytic stage of C felis. In 2 studies,6,7 investigators confirmed that monocytes were the infected cells in the leukocytic stage of the disease. Interstitial pneumonia commonly evident in cats that die of C felis infection has been described and categorized, and the author of that report8 suggested that this inflammation is likely caused by release of proinflammatory cytokines and chemokines by the infected monocytes. One of the main histopathologic characteristics of cytauxzoonosis is the presence of giant, infected, intravascular monocytes, many of which are adhered to the vascular endothelium and that possibly have involvement with and cause activation of CD18.
The CD18 integrin is present on most leukocytes, especially when they are activated,9–19 and this integrin plays a role in the adherence of leukocytes to the endothelium during inflammation. Different molecules, such as chemokines, fibrinogen, selectins, and cytokines such as TNF-α, can activate integrins. Chemokines are among the most important and common activating molecules for integrins.15,16,18–21
The objective of the study reported here was to characterize the systemic immune response of cats to C felis infection. We hypothesized that uncontrolled proinflammatory immune responses, caused in part by increased CD18 expression, contribute to the pathogenesis of cytauxzoonosis.
Black hole quencher-1
Glyceraldehyde 3-phosphate dehydrogenase
Lower limit of detection
Quantitative real-time reverse transcription
Serum protein electrophoresis
Tumor necrosis factor
PAXgene blood tube, Qiagen, Valencia, Calif.
DuoSet, RnD Systems, Minneapolis, Minn.
Nunc-Immuno, Sigma-Aldrich, St Louis, Mo.
KC4, BioTek, Winooski, Vt.
Animal Health Diagnostic Center, Cornell University, Ithaca, NY.
Dako Envision system, Dako, Carpinteria, Calif.
Clone AA124, AbD Serotec, Raleigh, NC.
L.A.B. solution, Polysciences, Warrington, Pa.
Clone Fe3.9F2, provided by Dr. Peter Moore, Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, Calif.
Clone M-18, Santa Cruz Biotechnology, Santa Cruz, Calif.
PAXgene blood RNA kit, Qiagen, Valencia, Calif.
ThermoScript RT-PCR system, Invitrogen, Grand Island, NY.
NanoDrop 2000, Thermo Scientific, Waltham, Wash.
Integrated DNA Technologies, Coralville, Iowa.
Primer3, Broad Institute, Cambridge, Mass. Available at: www.genome.wi.mit.edu/genome_software/other/primer3.html. Accessed Mar 1, 2009.
iCycler IQ system, Bio-Rad, Hercules, Calif.
Excel 2007, Microsoft Corp, Redmond, Wash.
InStat, GraphPad Software Inc, La Jolla, Calif.
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