Influence of Two Major Toxoplasma Gondii Virulence Factors (ROP16 and ROP18) on the Immune Response of Peripheral Blood Mononuclear Cells to Human Toxoplasmosis Infection

Abstract

Toxoplasma gondii ROP16 and ROP18 proteins have been identified as important virulence factors for this parasite. Here, we describe the effect of ROP16 and ROP18 proteins on peripheral blood mononuclear cells (PBMCs) from individuals with different clinical status of infection. We evaluated IFN-γ, IL-10, and IL-1β levels in supernatants from PBMCs cultures infected with tachyzoites of the T. gondii wild-type RH strain or with knock-out mutants of the rop16 and rop18 encoding genes (RHΔrop16 and RHΔrop18). Cytokine secretion was compared between PBMCs obtained from seronegative individuals (n = 10), with those with chronic asymptomatic (n = 8), or ocular infection (n = 12). We also evaluated if polymorphisms in the genes encoding for IFN-γ, IL-10, IL-1β, Toll-like receptor 9 (TLR9), and purinoreceptor P2RX7 influenced the production of the encoded proteins after ex vivo stimulation. In individuals with chronic asymptomatic infection, only a moderate effect on IL-10 levels was observed when PBMCs were infected with RHΔrop16, whereas a significant difference in the levels of inflammatory cytokines IFN-γ and IL-1β was observed in seronegative individuals, but this was also dependent on the host's cytokine gene polymorphisms. Infection with ROP16-deficient parasites had a significant effect on IFN-γ production in previously non-infected individuals, suggesting that ROP16 which is considered as a virulence factor plays a role during the primary infection in humans, but not in the secondary immune response.

Treatment Strategy in Human Ocular Toxoplasmosis: Why Antibiotics Have Failed

“…Thus, about 3 million individuals in Europe suffer active OT or carry corresponding scars, in many instances in the absence of a known history of OT. Clinical disease severity is usually mild to moderate and driven by a balance between parasite virulence [ 9 , 10 ] and host immunity [ 11 , 12 ].…”

The Epidemiology of Zoonotic Parasites of Farm Animals and Birds in China in the Past Ten Years

“…Since then, people have recognized Toxoplasmosis. Toxoplasmosis is a worldwide zoonotic parasitic disease, caused by Toxoplasma gondii of the genus Toxoplasma (Hernández-de-Los- Ríos et al 2019). This intracellular parasite can infect humans and almost all warm-blooded animals, including mammals and birds.…”

The Constant Threat of Zoonotic and Vector-Borne Emerging Tropical Diseases: Living on the Edge

“…The impact of these diseases and the establishment of local transmission in traditionally non-endemic areas, due to migration and travel, have been revealed over the last years. Diseases such as Chikungunya (11-16), Zika (17-24), Yellow Fever (25-28), Dengue (29)(30)(31)(32)(33), Oropouche, Madre de Dios virus, Iquitos virus (34,35), Mayaro Fever (36,37), Ebola (38)(39)(40)(41)(42), Nipah virus, arenaviruses such as Lassa (43), Machupo (44,45), Chapare (45,46), Junin (47), zoonotic Malaria (48), Severe Fever with Thrombocytopenia Syndrome (49), Plague (50), Crimean-Congo Hemorrhagic Fever, Acute Orally Transmitted Chagas Disease (51)(52)(53)(54), Visceral and Diffuse Cutaneous Leishmaniasis (55,56), Toxoplasmosis (57)(58)(59), Tick-Borne Diseases (60,61), Rift Valley Fever, Tuberculosis (62), Leprosy (63)(64)(65)(66)(67), Avian Influenza (68)(69)(70), Orthohantavirus (71)(72)…”

“…The impact of these diseases and the establishment of local transmission in traditionally non-endemic areas, due to migration and travel, have been revealed over the last years. Diseases such as Chikungunya ( 11 – 16 ), Zika ( 17 – 24 ), Yellow Fever ( 25 – 28 ), Dengue ( 29 – 33 ), Oropouche, Madre de Dios virus, Iquitos virus ( 34 , 35 ), Mayaro Fever ( 36 , 37 ), Ebola ( 38 – 42 ), Nipah virus, arenaviruses such as Lassa ( 43 ), Machupo ( 44 , 45 ), Chapare ( 45 , 46 ), Junin ( 47 ), zoonotic Malaria ( 48 ), Severe Fever with Thrombocytopenia Syndrome ( 49 ), Plague ( 50 ), Crimean-Congo Hemorrhagic Fever, Acute Orally Transmitted Chagas Disease ( 51 – 54 ), Visceral and Diffuse Cutaneous Leishmaniasis ( 55 , 56 ), Toxoplasmosis ( 57 – 59 ), Tick-Borne Diseases ( 60 , 61 ), Rift Valley Fever, Tuberculosis ( 62 ), Leprosy ( 63 – 67 ), Avian Influenza ( 68 – 70 ), Orthohantavirus ( 71 – 75 ), and Toxocariasis ( 76 , 77 ) have posed a significant impact to human health. Furthermore, zoonotic epidemics and pandemic coronaviruses, such as the Severe Acute Respiratory Syndrome (SARS), the Middle East Respiratory Syndrome (MERS) ( 78 – 82 ), and the ongoing SARS-CoV-2/COVID-19 ( 83 , 84 ) pandemic, have caused a profound economical and social disruption threatening to overwhelm public health systems globally ( 85 ) ( Table 1 ).…”