Despite the key role that antibodies play in protection, the cellular processes mediating the acquisition of humoral immunity against malaria are not fully understood. Using an infection model of severe malaria, we find that germinal center (GC) B cells upregulate the transcription factor T-bet during infection. Molecular and cellular analyses reveal that T-bet in B cells is required not only for IgG2c switching but also favors commitment of B cells to the dark zone of the GC. T-bet was found to regulate the expression of Rgs13 and CXCR3, both of which contribute to the impaired GC polarization observed in the absence of T-bet, resulting in reduced IghV gene mutations and lower antibody avidity. These results demonstrate that T-bet modulates GC dynamics, thereby promoting the differentiation of B cells with increased affinity for antigen.
Toxoplasmosis was studied in 102 families, in which index-cases manifested the fully symptomatic course of the acquired lymphnodular toxoplasmosis, confirmed by presence of IgM and IgG class antibodies (ELISA, Vidas, BioMerieux). The index-cases (group A) provided a rational index of the acquired invasion or its late sequele in other families members. The studies were performed in 388 persons, originating from Wielkopolska region, including 102 patients of a group A and 286 of families members of group B (167 children and 221 adults). In group A patients (including 49 children and 53 adults) immunoserological studies detected IgM class antibodies in 68.7% of cases and IgG class antibodies in 94.1% patients. In 286 family members (group B), presence of IgM class antibodies was found in 12.2% and IgG class antibodies was found in 55.2% studied persons; clinical pathology was noted in 46 patients (16.3%) including 3 pregnant women. The obtained results point to the need of complex evaluation of family environments based on analysis of serological tests (including estimation of IgM and IgG class antibodies) and accompanied by clinical analysis of studied children and adults.
Plasmodium falciparum , which causes malaria, extensively remodels its human host cells, particularly erythrocytes. Remodelling is essential for parasite survival by helping to avoid host immunity and assisting in the uptake of plasma nutrients to fuel rapid growth. Host cell renovation is carried out by hundreds of parasite effector proteins that are exported into the erythrocyte across an enveloping parasitophorous vacuole membrane (PVM). The Plasmodium translocon for exported (PTEX) proteins is thought to span the PVM and provide a channel that unfolds and extrudes proteins across the PVM into the erythrocyte. We show that exported reporter proteins containing mouse dihydrofolate reductase domains that inducibly resist unfolding become trapped at the parasite surface partly colocalizing with PTEX. When cargo is trapped, loop‐like extensions appear at the PVM containing both trapped cargo and PTEX protein EXP2, but not additional components HSP101 and PTEX150. Following removal of the block‐inducing compound, export of reporter proteins only partly recovers possibly because much of the trapped cargo is spatially segregated in the loop regions away from PTEX. This suggests that parasites have the means to isolate unfoldable cargo proteins from PTEX‐containing export zones to avert disruption of protein export that would reduce parasite growth.
A clinical and an epidemiological analysis was presented of a trichinellosis focus from Wielkopolska region. The studies included 20 persons and trichinellosis was diagnosed in 15 cases. The focus was characterized by asynchronous invasion with Trichinella sp. in individual affected persons in the course of a prolonged period (around 2.5 months) and by reporting of the patients to the Clinic during approximately 30 to 90 days after the disease signs/symptoms developed. Retrospective analysis and a set of specialized tests permitted to clarify causes of persisting complaints, presented by the patients, as well as to establish the diagnosis at late stages of trichinellosis.
Abstract Emerging evidence started to delineate multiple layers of memory B cells, with distinct effector functions during recall responses. Whereas most studies examining long-lived memory B cell responses have focussed on the IgG + memory B cell compartment, IgM + memory B cells have only recently started to receive attention. It has been proposed that unlike IgG + memory B cells, which differentiate into antibody-secreting plasma cells upon antigen re-encounter, IgM + memory B cells might have the additional capacity to establish secondary germinal centre (GC) responses. The precise function of IgM + memory B cells in the humoral immune response to malaria has not been fully defined. Using a murine model of severe malaria infection and adoptive transfer strategies we found that IgM + memory B cells induced in responses to P. berghei ANKA readily proliferate upon re-infection and adopt a GC B cell-like phenotype. The results suggest that that IgM + memory B cells might play an important role in populating secondary GCs after re-infection with Plasmodium, thereby initiating the induction of B cell clones with enhanced affinity for antigen, at faster rates than naive B cells.
IFN-γ-driven responses to malaria have been shown to modulate the development and function of T follicular helper (TFH) cells and memory B cells (MBCs), with conflicting evidence of their involvement in the induction of antibody responses required to achieve clinical immunity and their association with disease outcomes. Using high-dimensional single-cell mass cytometry, we identified distinct populations of TH1-polarized CD4+ T cells and MBCs expressing the TH1-defining transcription factor T-bet, associated with either increased or reduced risk of Plasmodium vivax (P. vivax) malaria, demonstrating that inflammatory responses to malaria are not universally detrimental for infection. Furthermore, we found that, whereas class-switched but not IgM+ MBCs were associated with a reduced risk of symptomatic malaria, populations of TH1 cells with a stem central memory phenotype, TH17 cells, and T regulatory cells were associated with protection from asymptomatic infection, suggesting that activation of cell-mediated immunity might also be required to control persistent P. vivax infection with low parasite burden.
Clinical and serological analysis was conducted on 102 families including index-cases of lymphonodular toxoplasmosis (102 patients-group A) and 286 family members (group B). The studies included a total of 388 persons (167 children and 221 adults), originating mainly from Wielkopolska region (West Poland). The lymphonodular form of toxoplasmosis represented the dominating pattern among adult cases but among children the clinical pathology pattern was variable: in 14 out of 49 children (group A) lymphadenopathy was not dominating sign and clinically signs and symptoms of central nervous system or organ of vision involvement prevailed; in 6 cases clinical pattern pointed to congenital toxoplasmosis and in 8 cases it indicated sequele of acquired toxoplasmosis. In group B, among 35 children with lymphadenopathy, 7 presented also neurological signs/symptoms, in 5 children the pattern suggested acquired neurotoxoplasmosis in 2 cases congenital form of toxoplasmosis. In 11 adults of the group, lymphonodular form of the disease was diagnosed. In both groups (A and B), the pattern lymphonodular toxoplasmosis was detected also in 5 pregnant women (1.3% of studied persons and 2.7% of all adults). Four of the pregnant women manifested active stage of the disease, confirmed by the presence of IgM class antibodies. Thus, among 286 family members clinical pathology was demonstrated in 46 patients (16.1%) and in 35 patients (12.2%) activity of the disease presented indications for a specialistic therapy.
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