Changes in the immune system in experimental acanthamoebiasis in immunocompetent and immunosuppressed hosts

Abstract

BackgroundAcanthamoebiasis is most often found in patients with immune deficiency, with infections facilitated by the intake of immunosuppressive drugs. The host immune response to Acanthamoeba spp. infection is poorly understood. Thus, in this study, we aimed to examine the course of Acanthamoeba spp. infection taking into account the host’s immunological status, including assessment of the hematological parameters, cytokine analysis, immunophenotypic changes in spleen populations, and histological spleen changes, which could help clarify some aspects of the immune response to acanthamoebiasis. In our experimental study, we used Acanthamoeba strain AM 22 isolated from the bronchoaspirate of a patient with acute myeloid leukaemia (AML) and atypical pneumonia symptoms.ResultsAcanthamoeba spp. affected the hematological parameters in immunocompetent and immunosuppressed mice and induced a change in spleen weight during infection. Moreover, analysis of anti-inflammatory (IL-4 and IL-10) and pro-inflammatory (IL-17A and IFN-γ) cytokines produced by splenocytes stimulated with concanavalin A demonstrated that Acanthamoeba spp. induced a selective Th1, Th2 and Th17 response at later stages of the infection in immunocompetent hosts. In the case of hosts with low immunity, Acanthamoeba elicited robust Th1 cell-mediated immunity without the participation of Th17. We observed suppression of CD8+ and CD4+ T lymphocytes and CD3+CD4-CD8- double-negative (DN) T lymphocyte populations in the beginning, and in the case of CD3+/CD4+/CD8+ double-positive (DP) T cells in the final phase of Acanthamoeba spp. infection in hosts with low immunity. Also, CD4+T lymphocytes and CD3+/CD4+ and CD3+/CD8+ lymphocyte counts during each stage of acanthamoebiasis were shown to be upregulated.ConclusionsWe demonstrated that analysis of the immune response and pathogenesis mechanisms of clinical isolates of Acanthamoeba spp. in an animal model not only has purely cognitive significance but above all, may help in the development of effective methods of pharmacological therapy especially in patients with low immunity.

Antioxidant defense in the eyes of immunocompetent and immunosuppressed mice infected with Acanthamoeba spp.

“…increased ability to produce IL-12, which differentiates T lymphocytes towards Th1 lymphocytes. Łanocha-Arendarczyk et al [42] found Th1 induction in Acanthamoeba spp. in the immunocompetent and immunosuppressive hosts.…”

“…We speculate that histopathological Fig. 4 Diagram of possible pathways of pathomechanism of disseminated acanthamoebiasis with eye infection [14,42,47,50,51] Abbreviations: BDNF, brain-derived neurotrophic factor; CD, cluster of differentiation; CNS; central nervous system; DAMPs, damage-associated molecular patterns; IL, interleukin; INF-α, interferon alpha; MMP-9, matrix metalloproteinases 9; NT-4, neurotrophin 4; ROS, reactive oxygen species; TIMP-1; tissue inhibitor of metalloproteinases 1; TLR, Toll like receptors; TNF-α, tumor necrosis factor alpha changes in the retina induced by increased ROS may contribute to a release of damage-associated molecular patterns (DAMPs) and activation of Toll-like receptors, as shown by changes in the expression of TLR2 and TLR4 in mice eyeballs with disseminated acanthamoebiasis [14]. However, TLRs can also be activated directly by Acanthamoeba spp.…”

Expression of Toll-Like Receptors (TLR2 and TLR4) in the Eyes of Mice Intranasally Infected with <em>Acanthamoeba</em> sp.

“…In our earlier studies on generalized acanthamoebiasis, induction of Th1, Th2, and Th17 expression was seen in immunocompetent hosts in the late stages of Acanthamoeba sp. infection, whereas in hosts with suppressed immunity, we observed a strong Th1 response, without Th17 [21].…”

The Expression of TLR2 and TLR4 in the Kidneys and Heart of Mice Infected with Acanthamoeba Spp.

“…In our earlier study concerning hematological and biochemical pro les in the blood of experimentally Acanthamoeba spp. infected mice, we found only higher level of lymphocytes, monocytes, thrombocytes and aspartate aminotransferase [7,8], despite the re-isolation of these amoebae from the brain, eyeball, lungs, kidneys, spleen and heart of the mice [7-11, unpublished data]. In another study concerning histopathological changes in the kidneys and heart of mice infected with Acanthamoeba spp., we observed some histopathological changes, including relaxation of muscle bres, elevated proliferation of cellular nuclei in the proximal/distal tubule epithelium and areas with less acidic cytoplasm [unpublished data].…”

“…activate the classical TLR signaling pathway inducing NF-kB activation and increased secretion of in ammatory cytokines [25]. Induction of an in ammatory response by amoebas has been proposed as an important factor to determine the course of the parasite infection [8]. Nevertheless, little is known about the innate immune response induced by Acanthamoeba spp.…”