Germinal center architecture disturbance during Plasmodium berghei ANKA infection in CBA mice

Abstract

BackgroundImmune responses to malaria blood stage infection are in general defective, with the need for long-term exposure to the parasite to achieve immunity, and with the development of immunopathology states such as cerebral malaria in many cases. One of the potential reasons for the difficulty in developing protective immunity is the poor development of memory responses. In this paper, the potential association of cellular reactivity in lymphoid organs (spleen, lymph nodes and Peyer's patches) with immunity and pathology was evaluated during Plasmodium berghei ANKA infection in CBA mice.MethodsCBA mice were infected with 1 × 106 P. berghei ANKA-parasitized erythrocytes and killed on days 3, 6–8 and 10 of infection. The spleen, lymph nodes and Peyer's patches were collected, fixed in Carson's formalin, cut in 5 μm sections, mounted in glass slides, stained with Lennert's Giemsa and haematoxylin-eosin and analysed with bright-field microscopy.ResultsEarly (day 3) strong activation of T cells in secondary lymphoid organs was observed and, on days 6–8 of infection, there was overwhelming activation of B cells, with loss of conventional germinal center architecture, intense centroblast activation, proliferation and apoptosis but little differentiation to centrocytes. In the spleen, the marginal zone disappeared and the limits between the disorganized germinal center and the red pulp were blurred. Intense plasmacytogenesis was observed in the T cell zone.ConclusionThe observed alterations, especially the germinal center architecture disturbance (GCAD) with poor centrocyte differentiation, suggest that B cell responses during P. berghei ANKA infection in mice are defective, with potential impact on B cell memory responses.

Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease

“…In agreement with previous studies (32,33), spleen sections from P. berghei ANKA-infected WT mice displayed a disturbed white pulp structure, with an important loss of T cells from the white pulp and a disorganized follicular mantle (Fig. 6D).…”

“…Our results in this study are consistent with those findings, as the increased pre-Tfh cell compartment found in CXCL10 2/2 mice was accompanied by increased numbers of isotype-switched, shortlived plasma cells and parasite-specific IgG Abs required for the control of parasitemia. Malaria infections have been shown to be accompanied by changes in splenic architecture (32,33,(46)(47)(48), including dissolution of the marginal zone, poor GC formation, and the loss of T cells from the white pulp. Because changes in the location of cells may affect access to Ag and cellular interactions, it has been proposed that this loss of secondary lymphoid organ structure affects the induction of immune responses.…”

cGAS-mediated control of blood-stage malaria promotes Plasmodium-specific germinal center responses

“…We have previously observed profound effects of blood-stage infection on the development of liver-stage-specific germinal center and memory formation (38). Plasmodium infection has been associated with ongoing splenic disruption in mice, monkeys, and humans (52)(53)(54)(55)(56). We hypothesized that the reduced GC function we observed in cGAS -/-mice could therefore be due to indirect effects from exacerbated infection.…”

Acute Plasmodium chabaudi Infection Dampens Humoral Responses to a Secondary T-Dependent Antigen but Enhances Responses to a Secondary T-Independent Antigen

“…Kinyanjui et al (38) showed that IgG responses in Kenyan children following (41) showed that human B cell memory and long-lived Ab levels expand gradually with repeated infections. In mice, although some studies have shown normal development of memory B cell responses during Plasmodium infection (22,42), others have shown defects in memory B cell generation or maintenance (43,44). Crompton and colleagues (45) also have suggested that P. falciparum drives short-lived plasma cell responses, which may explain why Ab levels are not maintained in the absence of repeated exposures, and because memory B cell and plasma cell responses are regulated independently of each other, the presence of memory B cells may not be required to maintain serum Ab levels.…”

“…However, it is clear that infection with Plasmodium affects the architecture of the spleen (30), which is a key immune induction site for blood-borne pathogens. Carvalho et al (43) observed that GCs in the spleen lost their conventional structure following infection with Plasmodium berghei and reported extrafollicular development of plasmablasts. In addition, extrafollicular B cell activation has been reported for P. chabaudi (57) and other parasite infections (58).…”