Sialylated N-glycan profile during acute and chronic infections with Toxoplasma gondii in mice

Abstract

Toxoplasma gondii is associated with physiological and psychiatric perturbations. The immune response is interrelated to the progress of anhedonia and despair symptoms of T. gondii-infected subjects. We recently reported that serum N-glycans were altered in mice displayed depressive-like behaviors. However, a novel biomarker that correlated to T. gondii infection and associated behaviors is demanded. Glycomics has been used to find affected glycoproteins during depression. The objective of this study is to investigate serum N-glycomics changes during infection with T. gondii in BALB/c mice, immunocompetent, or in severe combined immunodeficient mice, and after treatment with an immunostimulant; 1-methyl tryptophan. Glycans were examined through glycoblotting-protocol then investigated by MALDI-TOF/MS. Both depressive and sickness-related behaviors were significantly abundant (P ≤ 0.001 each), during acute T. gondii in immunocompetent mice, compared to controls. Only sickness symptoms were evident in immunodeficient mice infected with T. gondii, as associated with high expression level (P ≤ 0.001) of Peak # 15 (2 × Neu5Gc) compared to controls. The alteration of sialylated N-glycan expressions is important to detect the immune status of animals/humans against T. gondii. Moreover, 1-methyl tryptophan reduced depressive-like behavior (P ≤ 0.001) compared to controls. Therefore, sialylated N-glycan (Neu5Ac/Neu5Gc-terminal) is targeted to be used as a novel biomarker of sickness/depressive-like behaviors. Toxoplasma gondii affects all warm-blooded animals and infects almost one-third of all humans. T. gondii infection is a parasitic disease prevalent worldwide and involved in many psychiatric disorders 1. Moreover; depression is considered as one of the major psychological disorders and the global root of disability in the 21 st century 2. It is defined as a mood disorder due to the reduction of interest, happiness, learning abilities, sleep, appetite, and energy 3. Several studies had shown that seroprevalence of T. gondii in neuropsychiatric defects were variable like schizophrenia, bipolar mood disorder 4 and self-directed violence 5. Challenge with T. gondii revealed two characteristic forms: immune-stimulating tachyzoites and immune-encrypted bradyzoites. Recent studies had demonstrated that the brain is an immune-privileged region of residence of bradyzoite cysts 6. Hence, the pathogenesis of infection depends mainly upon host immunity activated macrophages and lymphocytes immediately primed to kill intracellular tachyzoites 7. However, under lowered immunity, the propagation of tachyzoites can be quite high as shown in immune-competent individuals 8 , which may result in fatal toxoplasmic encephalitis 9. T. gondii

Neurological and Neurobehavioral Disorders Associated with Toxoplasma gondii Infection in Humans

“…However, in a study conducted by Mahmoud et al, depression was correlated to reactivated T. gondii and not chronic infection of T. gondii in BALB/c mice [ 106 ]. In a study conducted in 2020, a similar result was found where chronic infection of T. gondii did not appear to have correlation with depression, yet there was a correlation with the acute stage [ 107 ]. Multiple other studies found no association between latent T .…”

Alteration of rhesus macaque serum N-glycome during infection with the human parasitic filarial nematode Brugia malayi

“…Rhesus macaques, in particular have shown high similarities with humans in terms of lymphatic pathology and immune responses 38 , 39 . However, application of serum or IgG glycoprofiling for infectious diseases has focused mostly on infection with viral or bacterial pathogens 22 , 47 with very few studies addressing infections with eukaryotic parasites such as protozoa 48 – 50 or metazoan flatworms and nematodes 48 , 51 , 52 .…”

Serum N-Glycome Diversity in Teleost and Chondrostrean Fishes

“…These glycans have been shown to modulate interactions between cells, between cells and their tissue micro-environment, as well as to mediate immune cell and growth factor signaling ( Ohtsubo and Marth, 2006 ; Moremen et al, 2012 ). Pronounced changes in the structure of the glycans attached to lipids and proteins have been reported in tissue development and disease progression in humans as well as model organisms such as zebrafish, fruit flies, and mice ( Wang et al, 2001 ; Nakakita et al, 2005 ; Ten Hagen et al, 2009 ; Baas et al, 2011 ; Chu et al, 2013 ; Hanzawa et al, 2017 ; Frappaolo et al, 2018 ; Cervoni et al, 2020 ; Rehan et al, 2020 ).…”