The role of autonomously secreted PGE2 and its autocrine/paracrine effect on bone matrix mineralization at the different stages of differentiating MC3T3-E1 cells.

Bone is consisted of osteoblast-linage cells, bone-forming cells in various differentiation stages. However, it is not fully understood how communicate and interact these cells immigrated from bone marrow. In this study, we showed that prostaglandin E2 (PGE2) had a role in autonomous modification of matrix mineralization in osteoblastic cell line, MC3T3-E1, and interactions across the cells in different differentiation stages. Analysis using LC-MS/MS and inhibitors showed the autonomous secretion of PGE2 among the prostanoids in differentiation stages and that depend on COX-2, a key enzyme for production of PGE2. Treatment with inhibitors of PGE2 receptors and COX-2 indicated that secreted PGE2 regulates matrix mineralization in an autocrine/paracrine manner. In addition, we showed that the expression profile of PGE2 receptors (EP1-EP4) and PGE2 effects on matrix mineralization derived from it changed during cell differentiation. Treatment with inhibitors of PGE2 signaling in the early differentiation stage of MC3T3-E1 cells induced significant changes in matrix mineralization several days after. Stimulation with the extracts from culture medium of the matured cells including PGE2 and co-culture with the matured cells secreting PGE2 significantly promoted matrix mineralization of the early stage cells, in contrast, treatment with inhibitor of COX-2 and PGE2 receptors failed to do so. These results support that PGE2 plays important roles in the interaction system of osteoblast-linage cells in bone tissue to regulate matrix mineralization reflecting condition of bone-forming cells, that is, population and maturation.

Asymptomatic malaria, growth status, and anaemia among children in Lao People's Democratic Republic: a cross-sectional study.

BACKGROUND: Asymptomatic malaria can be observed in both stable endemic areas and unstable transmission areas. However, although much attention has been given to acute malaria infections, relatively little attention has been paid to asymptomatic malaria. Nonetheless, because the asymptomatic host serves as a reservoir for the malaria parasite, asymptomatic malaria is now recognized as an important obstacle to malaria elimination. Asymptomatic malaria is also associated with anaemia, a global public health problem with serious consequences on human health as well as social and economic development. In Lao People's Democratic Republic (Lao PDR), malaria, anaemia, and malnutrition are serious public health concerns. However, few studies have focused on the relationship between these variables. Therefore, this study investigated the relationship between asymptomatic malaria, growth status, and the prevalence of anaemia among children aged 120 months old or younger in rural villages in Lao PDR. METHODS: In December 2010 and March 2011, data were collected from five villages in Savannakhet province. Anthropometric measurements, blood samples, and malaria rapid diagnostic tests were conducted. The presence of malaria was confirmed with polymerase chain reaction assays for Plasmodium falciparum. Underweight status, stunting, and anaemia were defined according to World Health Organization standards. RESULTS: The mean age of participants (n = 319) was 88.3 months old (Standard Deviation: 20.6, ranged from 30-119 months old), and 20 participants (6.3 %) had an asymptomatic malaria infection, 92 (28.8 %) were anaemic, 123 (38.6 %) were underweight, and 137 (42.9 %) were stunted. Stunted children were more likely to be infected with asymptomatic malaria [odds ratio (OR) 3.34, 95 % confidence interval (CI) 1.25-8.93], and asymptomatic malaria was associated with anaemia [OR 5.17, 95 % CI 1.99-13.43]. CONCLUSIONS: These results suggest a significant association between asymptomatic malaria and anaemia in children. Furthermore, stunted children were more likely to have lower Hb levels and to be infected with asymptomatic malaria than children without stunting. However, further studies examining the impact of asymptomatic malaria infection on children's nutritional and development status are necessary.

IL-23 protection against Plasmodium berghei infection in mice is partially dependent on IL-17 from macrophages.

Although IL-12 is believed to contribute to protective immune responses, the role played by IL-23 (a member of the IL-12 family) in malaria is elusive. Here, we show that IL-23 is produced during infection with Plasmodium berghei NK65. Mice deficient in IL-23 (p19KO) had higher parasitemia and died earlier than wild-type (WT) controls. Interestingly, p19KO mice had lower numbers of IL-17-producing splenic cells than their WT counterparts. Furthermore, mice deficient in IL-17 (17KO) suffered higher parasitemia than the WT controls, indicating that IL-23-mediated protection is dependent on induction of IL-17 during infection. We found that macrophages were responsible for IL-17 production in response to IL-23. We observed a striking reduction in splenic macrophages in the p19KO and 17KO mice, both of which became highly susceptible to infection. Thus, IL-17 appears to be crucial for maintenance of splenic macrophages. Adoptive transfer of macrophages into macrophage-depleted mice confirmed that macrophage-derived IL-17 is required for macrophage accumulation and parasite eradication in the recipient mice. We also found that IL-17 induces CCL2/7, which recruit macrophages. Our findings reveal a novel protective mechanism whereby IL-23, IL-17, and macrophages reduce the severity of infection with blood-stage malaria parasites.

Babesia microti alleviates disease manifestations caused by Plasmodium berghei ANKA in murine co-infection model of complicated malaria.

Malaria remains one of the most significant health issues worldwide, accounting for 2.6% of the total global disease burden, and efforts to eliminate this threat continue. The key focus is to develop an efficient and long-term immunity to this disease via vaccination or therapeutic approach, and innovative strategies would enable us to achieve this target. Previously, using a mouse co-infection disease model, cross-protection was illustrated between Babesia microti and Plasmodium chabaudi. Hence, this study was planned to elucidate the impact of acute B. microti Peabody mjr and Plasmodium berghei ANKA co-infection on the consequence of complicated malaria in the C57BL/6J mouse model of malaria. Furthermore, immune response and pathological features were analyzed, and the course of the disease was compared among experimental groups. Our study established that acute B. microti infection activated immunity which was otherwise suppressed by P. berghei. The immunosuppressive tissue microenvironment was counteracted as evidenced by the enhanced immune cell population in co-infected mice, in contrast to P. berghei-infected control mice. Parasite sequestration in the brain, liver, lung, and spleen of co-infected mice was significantly decreased and tissue injury was ameliorated. Meanwhile, the serum levels of IFN-γ, TNF-α, and IL-12p70 were reduced while the secretion of IL-10 was promoted in co-infected mice. Eventually, co-infected mice showed an extended rate of survival. Hereby, the principal cytokines associated with the severity of malaria by P. berghei infection were TNF-α, IFN-γ, and IL-12p70. Moreover, it was evident from our flow cytometry results that innate immunity is crucial and macrophages are at the frontline of immunity against P. berghei infection. Our study recommended further investigations to shed light on the effects of babesiosis in suppressing malaria with the goal of developing Babesia-based therapy against malaria.

Protective function of an unconventional γδ T cell subset against malaria infection in apoptosis inhibitor deficient mice.

Various subsets of T-cell receptor (TCR) γδ⁺ T cells expressing distinct TCR-Vγ chains are found in many different anatomical locations. These TCR γδ⁺ T cells perform multiple functions as an essential part of the immune system. In particular, protection against malaria infection by TCR γδ⁺ T cells is of special interest. In the present study, we confirmed that the Vγ7⁺ γδ T cells, which are an unconventional subset usually localized within the intestine, are recruited to the liver and spleen at the late stage of malaria infection, and contribute to protection against malaria infection via a multifunctional approach in apoptosis inhibitor-deficient mice.

Effect of α-Tocopheryloxy Acetic Acid on the Infection of Mice with Plasmodium berghei ANKA In Vivo and Humans with P. falciparum In Vitro.

PURPOSE: Malarial parasites are susceptible to oxidative stress. The effects of α-tocopheryloxy acetic acid (α-TEA), a vitamin E analog, on infection by Plasmodium berghei ANKA and P. falciparum in mice and human red blood cells (RBCs), respectively, were examined in this study. METHODS: For in vivo studies in mice, RBCs infected with P. berghei ANKA were inoculated via intraperitoneal injection and α-TEA was administered to C57BL/6 J male mice after infection. The blood-brain barrier (BBB) permeability was examined by Evans blue staining in experimental cerebral malaria at 7 days after infection. The in vitro inhibitory effect of α-TEA on P. falciparum 3D7 (chloroquine-sensitive strain) and K1 (multidrug-resistant strain) was tested using a SYBR Green I-based assay. RESULTS: When 1.5% α-TEA was administered for 14 days after infection, 88% of P. berghei ANKA-infected mice survived during the experimental period. Nevertheless, all the control mice died within 12 days of infection. Furthermore, the Evans blue intensity in α-TEA-treated mice brains was less than that in untreated mice, indicating that α-TEA might inhibit the destruction of the BBB and progression of cerebral malaria. The in vitro experiment revealed that α-TEA inhibited the proliferation of both the 3D7 and K1 strains. CONCLUSION: This study showed that α-TEA is effective against murine and human malaria in vivo and in vitro, respectively. Although α-TEA alone has a sufficient antimalarial effect, future research could focus on the structure-activity relationship to achieve better pharmacokinetics and decrease the cytotoxicity and/or the combined effect of α-TEA with existing drugs. In addition, the prophylactic antimalarial activity of premedication with α-TEA may also be an interesting perspective in the future.

Natural Compounds Tapinarof and Galactomyces Ferment Filtrate Downregulate IL-33 Expression via the AHR/IL-37 Axis in Human Keratinocytes.

Interleukin (IL)-37 suppresses systemic and local inflammation. It is expressed in the epidermis, the external layer of the skin, and is decreased in inflammatory skin diseases including atopic dermatitis (AD) and psoriasis. Therefore, an agent applied topically on the skin that can increase IL-37 could be promising for treating AD and psoriasis; however, the mechanism regulating IL-37 remains largely unknown. Given that IL-37 expression is induced in differentiated keratinocytes, a major component of the epidermis, and that activation of aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, promotes keratinocyte differentiation, we hypothesized that AHR might be involved in the IL-37 expression in human keratinocytes. We analyzed normal epidermal human keratinocytes (NHEKs) treated with tapinarof and Galactomyces ferment filtrate (GFF), which are potent AHR modulators. We found that tapinarof and GFF upregulated IL-37 in NHEKs, which was canceled by the knockdown of AHR using siRNA transfection, indicating that AHR mediates IL-37 expression in NHEKs. Furthermore, we found that the knockdown of IL-37 resulted in the upregulation of IL-33, an alarmin cytokine with crucial roles in the pathogenesis of AD and psoriasis. These findings suggest that IL-37 negatively regulates IL-33 expression in NHEKs. Finally, we examined whether tapinarof and GFF treatment modulates IL-33 expression in NHEKs. Such treatment inhibited IL-33 expression, which was partially reversed by the knockdown of either AHR or IL-37. Taken together, our findings provide the first evidence that tapinarof and GFF could have potential to prevent IL-33-overexpressing disorders such as AD and psoriasis via the AHR/IL-37 axis.

The Antidiabetic Agent Metformin Inhibits IL-23 Production in Murine Bone-Marrow-Derived Dendritic Cells.

Psoriasis is a chronic inflammatory skin disease, and its immune mechanism has been profoundly elucidated. Biologics targeting interleukin (IL)-23 have prevented the development of psoriasis. As major sources of IL-23, dendritic cells (DCs) play a pivotal role in psoriasis; however, the regulatory mechanism of IL-23 in DCs remains unclear. IL-36γ was reported to reflect the disease activity of psoriasis. Therefore, we hypothesized that IL-36γ may affect IL-23 production in DCs. To reveal the mechanism by which IL-36γ controls IL-23 production in DCs, we analyzed murine bone marrow-derived DCs (BMDCs) stimulated with IL-36γ. IL-36γ stimulation upregulated the mRNA and protein expression of Nfkbiz in BMDCs. Nfkbiz knockdown using siRNA transfection partially inhibited the upregulation of IL-23 mRNA expression induced by IL-36γ stimulation. Since NF-κB signaling regulates Nfkbiz expression and the anti-diabetic agent metformin reportedly modulates NF-κB signaling, we examined the effect of metformin treatment on IL-36γ-induced IL-23 production. Metformin treatment impaired the phosphorylation of NF-κB induced by IL-36γ stimulation with the subsequent downregulation of Nfkbiz, resulting in the inhibition of IL-23 production in BMDCs. These data provided evidence that metformin treatment can inhibit IL-36γ-mediated IL-23 production in BMDCs, which might contribute to the prevention of psoriasis.

Author Correction: CD8+ T cell activation by murine erythroblasts infected with malaria parasites.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Fluctuations of Spleen Cytokine and Blood Lactate, Importance of Cellular Immunity in Host Defense Against Blood Stage Malaria Plasmodium yoelii.

Our previous studies of protective immunity and pathology against blood stage malaria parasites have shown that not only CD4+ T cells, but also CD8+ T cells and macrophages, are important for host defense against blood stage malaria infection. Furthermore, we found that Plasmodium yoelii 17XNL (PyNL) parasitizes erythroblasts, the red blood cell (RBC) precursor cells, which then express MHC class I molecules. In the present study, we analyzed spleen cytokine production. In CD8+ T cell-depleted mice, IL-10 production in early stage infection was increased over two-fold relative to infected control animals and IL-10+ CD3- cells were increased, whereas IFN-γ production in the late stage of infection was decreased. At day 16 after PyNL infection, CD8+ T cells produced more IFN-γ than CD4+ T cells. We evaluated the involvement of the immunoproteasome in induction of immune CD8+ T cells, and the role of Fas in protection against PyNL both of which are downstream of IFN-γ. In cell transfer experiments, at least the single molecules LMP7, LMP2, and PA28 are not essential for CD8+ T cell induction. The Fas mutant LPR mouse was weaker in resistance to PyNL infection than WT mice, and 20% of the animals died. LPR-derived parasitized erythroid cells exhibited less externalization of phosphatidylserine (PS), and phagocytosis by macrophages was impaired. Furthermore, we tried to identify the cause of death in malaria infection. Blood lactate concentration was increased in the CD8+ T cell-depleted PyNL-infected group at day 19 (around peak parasitemia) to similar levels as day 7 after infection with a lethal strain of Py. When we injected mice with lactate at day 4 and 6 of PyNL infection, all mice died at day 8 despite demonstrating low parasitemia, suggesting that hyperlactatemia is one of the causes of death in CD8+ T cell-depleted PyNL-infected mice. We conclude that CD8+ T cells might control cytokine production to some extent and regulate hyperparasitemia and hyperlactatemia in protection against blood stage malaria parasites.

Malaria protection in beta 2-microglobulin-deficient mice lacking major histocompatibility complex class I antigens: essential role of innate immunity, including gammadelta T cells.

It is still controversial whether malaria protection is mediated by conventional immunity associated with T and B cells or by innate immunity associated with extrathymic T cells and autoantibody-producing B cells. Given this situation, it is important to examine the mechanism of malaria protection in beta(2)-microglobulin-deficient (beta(2)m(-/-)) mice. These mice lack major histocompatibility complex class I and CD1d antigens, which results in the absence of CD8(+) T cells and natural killer T (NKT) cells. When C57BL/6 and beta(2)m(-/-) mice were injected with parasitized (Plasmodium yoelii 17XNL) erythrocytes, both survived from the infection and showed a similar level of parasitaemia. The major expanding T cells were NK1.1(-) alphabeta T-cell receptor(int) cells in both mice. The difference was a compensatory expansion of NK and gammadelta T cells in beta(2)m(-/-) mice, and an elimination experiment showed that these lymphocytes were critical for protection in these mice. These results suggest that malaria protection might be events of the innate immunity associated with multiple subsets with autoreactivity. CD8(+) T and NKT cells may be partially related to this protection.

A Unique Subset of γδ T Cells Expands and Produces IL-10 in Patients with Naturally Acquired Immunity against Falciparum Malaria.

Although expansions in γδ T cell populations are known to occur in the peripheral blood of patients infected with Plasmodium falciparum, the role of these cells in people with naturally acquired immunity against P. falciparum who live in malaria-endemic areas is poorly understood. We used a cross-sectional survey to investigate the role of peripheral blood γδ T cells in people living in Lao People's Democratic Republic, a malaria-endemic area. We found that the proportion of non-Vγ9 γδ T cells was higher in non-hospitalized uncomplicated falciparum malaria patients (UMPs) from this region. Notably, we found that the non-Vγ9 γδ T cells in the peripheral blood of UMPs and negative controls from this region had the potential to expand and produce IL-10 and interferon-γ when cultured in the presence of IL-2 and/or crude P. falciparum antigens for 10 days. Furthermore, these cells were associated with plasma interleukin 10 (IL-10), which was elevated in UMPs. This is the first report demonstrating that, in UMPs living in a malaria-endemic area, a γδ T cell subset, the non-Vγ9 γδT cells, expands and produces IL-10. These results contribute to understanding of the mechanisms of naturally acquired immunity against P. falciparum.

A possible origin population of pathogenic intestinal nematodes, Strongyloides stercoralis, unveiled by molecular phylogeny.

Humans and dogs are the two major hosts of Strongyloides stercoralis, an intestinal parasitic nematode. To better understand the phylogenetic relationships among S. stercoralis isolates infecting humans and dogs and to assess the zoonotic potential of this parasite, we analyzed mitochondrial Cox1, nuclear 18S rDNA, 28S rDNA, and a major sperm protein domain-containing protein genes. Overall, our analyses indicated the presence of two distinct lineages of S. stercoralis (referred to as type A and type B). While type A parasites were isolated both from humans and dogs in different countries, type B parasites were found exclusively in dogs, indicating that the type B has not adapted to infect humans. These epidemiological data, together with the close phylogenetic relationship of S. stercoralis with S. procyonis, a Strongyloides parasite of raccoons, possibly indicates that S. stercoralis originally evolved as a canid parasite, and later spread into humans. The inability to infect humans might be an ancestral character of this species and the type B might be surmised to be an origin population from which human-infecting strains are derived.

Activation of CD1d-independent NK1.1+ T cells in the large intestine by Lactobacilli.

Among digestive organs, the liver and the large intestine are abundant in T cells expressing NK1.1. NK1.1+ T cells in the liver are mostly CD1d-dependent whereas those in the large intestine are CD1d-independent. In this study, we investigated the effects of Lactobacilli on NK1.1+ T cells in the digestive organs of mice. C57BL/6 mice were orally given a dietary supplement prepared from mixed cultures of eight strains of Lactobacilli. Oral administration of Lactobacilli to mice resulted in the selective expansion of NK1.1+ T cells in the large intestine. These colon NK1.1+ T cells activated by Lactobacilli were found to express IFN-gamma mRNA. The level of IFN-gamma in the serum was also elevated by the administration of Lactobacilli. Our results suggest that Lactobacilli selectively activate CD1d-independent NK1.1+ T cells in the large intestine to produce IFN-gamma and therefore modulate Th1 immune responses.

Masses of Fluid for Cylindrical Tanks in Rock With Partial Uplift of Bottom Plate.

This study proposes the use of a slice model consisting of a set of thin rectangular tanks for evaluating the masses of fluid contributing to the rocking motion of cylindrical tanks; the effective mass of fluid for rocking motion, that for rocking-bulging interaction, effective moment inertia of fluid for rocking motion and its centroid. They are mathematically or numerically quantified, normalized, tabulated, and depicted as functions of the aspect of tanks for different values of the ratio of the uplift width of the tank bottom plate to the diameter of tank for the designer's convenience.

A transient resistance to blood-stage malaria in interferon-γ-deficient mice through impaired production of the host cells preferred by malaria parasites.

IFN-γ plays both pathological and protective roles during blood-stage malaria. One of its pathological roles is its contribution to anemia by suppressing erythropoiesis. Here, to evaluate the effects of IFN-γ-mediated alterations in erythropoiesis on the course of malaria infection, mice deficient in IFN-γ (GKO) were infected with two strains of the rodent malaria parasite Plasmodium yoelii, 17XL (PyL) and 17XNL (PyNL), whose host cell ranges differ. Regardless of genotype, all mice infected with PyL, which can invade any erythrocyte, developed high parasitemia and died quickly. Although PyNL caused a transient non-lethal infection in wild-type (WT) mice, some GKO mice were unable to control the infection and died. However, GKO mice were resistant to the early phase of infection, showing an impaired increase in parasitemia compared with WT mice. This resistance in the GKO mice was associated with having significantly fewer reticulocytes, which are the preferred host cells for PyNL parasites, than the WT mice. Compared with the amount of reticulocytes in GKO mice during the early stages of infection, there was a significant increase in the amount of these cells at later stages, which coincided with the inability of these mice to control the infection. We found that the growth of PyNL parasites correlated with the amount of reticulocytes. Thus, the reduced number of reticulocytes in mice lacking IFN-γ appears to be responsible for the limited parasite growth. Notably, these differences in GKO mice were at least partially reversed when the mice were injected with exogenous IFN-γ. Additionally, an artificial induction of hemolytic anemia and an increase in reticulocytes by phenylhydrazine treatment in GKO mice completely abolished the lower parasitemia and resistance during early phase infection. These results suggest that IFN-γ may contribute to the early growth of PyNL parasites by increasing the amount of reticulocytes, presumably by enhancing erythropoiesis.

Cytotoxic activities of CD8⁺ T cells collaborate with macrophages to protect against blood-stage murine malaria.

The protective immunity afforded by CD8(+) T cells against blood-stage malaria remains controversial because no MHC class I molecules are displayed on parasite-infected human erythrocytes. We recently reported that rodent malaria parasites infect erythroblasts that express major histocompatibility complex (MHC) class I antigens, which are recognized by CD8(+) T cells. In this study, we demonstrate that the cytotoxic activity of CD8(+) T cells contributes to the protection of mice against blood-stage malaria in a Fas ligand (FasL)-dependent manner. Erythroblasts infected with malarial parasites express the death receptor Fas. CD8(+) T cells induce the externalization of phosphatidylserine (PS) on the infected erythroblasts in a cell-to-cell contact-dependent manner. PS enhances the engulfment of the infected erythroid cells by phagocytes. As a PS receptor, T-cell immunoglobulin-domain and mucin-domain-containing molecule 4 (Tim-4) contributes to the phagocytosis of malaria-parasite-infected cells. Our findings provide insight into the molecular mechanisms underlying the protective immunity exerted by CD8(+) T cells in collaboration with phagocytes.

Plasmodium berghei ANKA causes intestinal malaria associated with dysbiosis.

Gastrointestinal symptoms, such as abdominal pain and diarrhea, are frequently observed in patients with Plasmodium falciparum malaria. However, the correlation between malaria intestinal pathology and intestinal microbiota has not been investigated. In the present study, infection of C57BL/6 mice with P. berghei ANKA (PbA) caused intestinal pathological changes, such as detachment of epithelia in the small intestines and increased intestinal permeability, which correlated with development with experimental cerebral malaria (ECM). Notably, an apparent dysbiosis occurred, characterized by a reduction of Firmicutes and an increase in Proteobacteria. Furthermore, some genera of microbiota correlated with parasite growth and/or ECM development. By contrast, BALB/c mice are resistant to ECM and exhibit milder intestinal pathology and dysbiosis. These results indicate that the severity of cerebral and intestinal pathology coincides with the degree of alteration in microbiota. This is the first report demonstrating that malaria affects intestinal microbiota and causes dysbiosis.

Evaluating experimental cerebral malaria using oxidative stress indicator OKD48 mice.

Cerebral malaria is a fatal complication of malaria. Conventional methods for evaluating experimental cerebral malaria have several drawbacks. Therefore, we aimed to develop an easy-to-use method for evaluating experimental cerebral malaria using OKD48 (Keap1-dependent Oxidative stress Detector, No-48-luciferase) mice to evaluate oxidative stress. OKD48 mice infected with Plasmodium berghei ANKA strain (PbA) suffered from experimental cerebral malaria and oxidative stress was successfully detected in the brains of living OKD48 mice developing experimental cerebral malaria. Oxidative stress in the brain was dependent on the development of experimental cerebral malaria, as prevention of experimental cerebral malaria did not elicit oxidative stress. We provide a novel evaluation method for experimental cerebral malaria using oxidative stress indicator OKD48 mice.

Induction of ssDNA-binding autoantibody secreting B cell immunity during murine malaria infection is a critical part of the protective immune responses.

Although it has been hypothesized that autoimmune-like phenomena may play a critical role in the protective immune responses to both human and animal malaria, there are still no evidence-based data to support this view. In this study we demonstrate that the majority of anti-single stranded (ss) DNA autoantibody secreting B cells were confined to B220(+)CD21(+)CD23(-) cells and that these cells expanded significantly in the spleen of C57BL/6 mice infected with Plasmodium yoelii 17X non-lethal (PyNL). To determine the role of ssDNA-binding autoantibody secreting B cell responses in murine malaria, we conjugated generation 6 (poly) amidoamine dendrimer nanoparticles with ssDNA to deplete ssDNA-binding autoreactive B cells in vivo. Our data revealed that 55.5% of mice died after DNA-coated nanoparticle-mediated in vivo depletion of ssDNA-specific autoreactive B cells and subsequent challenge using PyNL. Adoptive transfer of B cells with ssDNA specificity to mice, followed by PyNL infection, caused a later appearance and inhibition of parasitemia. The possible mechanism by which the ssDNA-binding autoantibody secreting B cells is involved in the protection against murine malaria has also been demonstrated.