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

Wilmore, Joel R.; Maue, Alexander C.; Lefebvre, Julie; Haynes, Laura; Rochford, Rosemary

doi:10.4049/jimmunol.1301450

Cited by 11 publications

(12 citation statements)

References 67 publications

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“…In models of autoimmunity, sepsis, or chronic inflammation, aberrant expansion of short-lived ASCs has been shown to disrupt the establishment and retention of a LLPC population (53–58). We found that accumulation of BM ASCs was defective in mice challenged with Δ srrAB 14 days earlier (Supplemental Figure 3E), and by 14 days post-challenge, no bacteria were found in the kidneys of mice from any group (data not shown) .…”

Section: Resultsmentioning

confidence: 99%

“…It is possible that the expansion of short-lived extrafollicular ASCs occurs at the expense of GC formation (53, 61). This could reduce the pool of ASCs selected for long-term survival in the BM since post-GC PCs likely have a selective advantage once they reach the BM (62).…”

Section: Resultsmentioning

confidence: 99%

“…Alternatively, they may lack the appropriate BCR signals required to upregulate CD138, or other as-yet-undefined receptors necessary for BM niche survival. This scenario would be similar to infection with Plasmodium chabaudi which drives an expanded T-independent ASC response while inhibiting long-term maintenance of the T-dependent Ab response (53). The fact that most of the expanded ASCs induced by SpA were surface IgM + may also be important if the genes expressed during formation of LLPC are downstream of BCR signaling through IgG, but not IgM (73).…”

Section: Discussionmentioning

confidence: 99%

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Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells

Keener

Thurlow

Kang

et al. 2017

The Journal of Immunology

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Infection with Staphylococcus aureus does not induce long-lived protective immunity for reasons that are not completely understood. Human and murine vaccine studies support a role for antibodies in protecting against recurring infections, but S. aureus modulates the B cell response through expression of Staphylococcal Protein A (SpA), a surface protein that drives polyclonal B cell expansion and induces cell death in the absence of co-stimulation. In this murine study, we show that SpA altered the fate of plasmablasts and plasma cells (PCs) by enhancing the short-lived extrafollicular response and reducing the pool of bone marrow (BM)-resident long-lived PCs (LLPCs). The absence of LLPCs was associated with a rapid decline in antigen-specific, class-switched antibody. In contrast, when previously inoculated mice were challenged with isogenic Δspa S. aureus, cells proliferated in the BM survival niches and sustained long-term antibody titers. The effects of SpA on PC fate were limited to the secondary response, as antibody levels and the formation of B cell memory occurred normally during the primary response in mice inoculated with either WT or Δspa S. aureus. Thus, failure to establish long-term protective antibody titers against S. aureus was not a consequence of diminished formation of B cell memory; instead, SpA reduced the proliferative capacity of PCs that entered the BM, diminishing the number of cells in the long-lived pool.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells

Keener

Thurlow

Kang

et al. 2017

The Journal of Immunology

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“…The data obtained in this work provide information that allows us to partially explain there is a delayed GC response and a significant reduction of the humoral response to Tdependent antigens 35 . Interestingly, we also observed that PD-L1 neg plasmablast functioned as an enhancers of T cell response ( Fig.4a and 4c) since in infected-chimera mice the frequency of PD-1 + IFN -+ TNF + -producing T cells was higher than in mice without plasmablast.…”

Section: Pd-l1 High Expression On Antibody-secreting Cells Was Previomentioning

confidence: 75%

PD-L1^hi plasmablasts limit the T cell response during the acute phase of parasite infections

Almada

et al. 2020

Preprint

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During infections with protozoan parasites or virus, T cell immunosuppression is generated simultaneously with a high B cell activation. Here, we show that in T. cruzi infection, all plasmablasts detected had higher surface expression of PD-L1, than other mononuclear cells. PD-L1 hi plasmablasts were induced in vivo in an antigen-specific manner and required help from Bcl-6 + CD4 + T cells. PD-L1 hi expression was not a characteristic of all antibody-secreting cells since plasma cells found during the chronic phase of infection express PD-L1 but at lower levels. PD-L1 hi plasmablasts were also present in mice infected with Plasmodium or with lymphocytic choriomeningitis virus, but not in mice with autoimmune disorders or immunized with T cell-dependent antigens. PD-L1 hi plasmablasts suppressed T cell response, via PD-L1, in vitro and in vivo. Thus, this study reveals that extrafollicular PD-L1 hi plasmablasts, which precede the germinal center (CG) response, are a suppressive population in infections that may influence T cell response. Brief summaryPathogens develop different strategies to settle in the host. We identified a plasmablats population induced by pathogens in acute infections which suppress T cell response. KEY WORDS RUNNING TITTLEPD-L1 + plasmablasts control T cell response to understand the delicate balance between protective T cell immunity, immune suppression and parasite establishment.Chagas disease presents an acute phase, both in mice and humans, characterized by a state of immunosuppression in which T. cruzi replicates extensively and induces immunomodulatory molecules that delay parasite-specific T cell effector responses 3-6 .It has been reported that during this phase of T. cruzi infection the expression of PD-1, one of the members of the CD28/CTLA4 family with inhibitory capacity, increases on myocardium infiltrating CD4 + and CD8 + T cells 7 . The cross-linking of PD-1 with any of its two ligands, PD-L1 8 or PD-L2 9 , inhibits the activation of T cells and the production of IL-2 and IFN Many studies have shown that other protozoan parasites such as Plasmodium spp. as well as bacteria and viruses also benefit from the PD-1/PD-L1 pathway to suppress and evade the host's adaptive immunity 10,11 . The activation of the PD-1/PD-L1 pathway would enable the establishment of microorganisms and chronicity [12][13][14] . Accordingly, the blocking of PD-1/PD-L1 signals, in combination with therapeutic immunizations or therapies with cytokines, has been proposed as a strategy to improve the efficacy of vaccinations 15 and to revitalize exhausted T cells 16 .During infection with T. cruzi, blocking PD-1 and PD-L1 or deletion of the PD-1 gene results in a reduction in parasitemia and tissue parasitism, but also increased mortality due to an augmented cardiac inflammatory response 7 . These results reveal that the signaling pathway of PD-1/PD-L1 has an important role in the control of inflammation induced by T. cruzi and provide another perspective on the mechanisms of regulation in the pathogenesis ...

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“…It is considered a genetically attenuated strain that is generated through many cycles within a mosquito vector, the intermediate host [ 15 , 16 ], which can quickly evolve into a more virulent form when in contact with the definitive host [ 17 ]. Studies have shown that there is an increase in the infectious process accompanied by the production of interferon gamma (IFNγ), which facilitates a response to TLR agonists, followed by an increase in serum IgG titers of cured mice [ 18 , 19 ]. Thus, the immune system provides malarial resistance in the infected animal through different mechanisms, which ensures a more efficient healing response [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Paradoxical sleep deprivation impairs mouse survival after infection with malaria parasites

Lungato

Gazarini

Paredes‐Gamero

et al. 2015

Malar J

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BackgroundParasitic diseases like malaria are a major public health problem in many countries and disrupted sleep patterns are an increasingly common part of modern life. The aim of this study was to assess the effects of paradoxical sleep deprivation (PSD) and sleep rebound (RB) on malarial parasite infection in mice.MethodsAfter PSD, one group was immediately infected with parasites (PSD). The two other PSD rebound groups were allowed to sleep normally for either 24 h (24 h RB) or 48 h (48 h RB). After the recovery periods, mice were inoculated with parasites.ResultsThe PSD group was the most affected by parasites presenting the higher death rate (0.02), higher number of infected cells (p < 0.01), and decrease in body weight (p < 0.04) compared to control and 48 h RB groups. The 24 h RB group was also different from control group in survival (p < 0.03), number of infected cells (p < 0.05) and body weight (p < 0.04). After 48 hours of sleep rebound animals were allowed to restore their response to parasitic infection similar to normal sleep animals.ConclusionsThese results suggest that PSD is damaging to the immune system and leads to an increased infection severity of malaria parasites; only 48 hours of recovery sleep was sufficient to return the mice infection response to baseline values.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0690-7) contains supplementary material, which is available to authorized users.

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

Cited by 11 publications

References 67 publications

Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells

Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells

PD-L1^hi plasmablasts limit the T cell response during the acute phase of parasite infections

Paradoxical sleep deprivation impairs mouse survival after infection with malaria parasites

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

Cited by 11 publications

References 67 publications

Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells

Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived Plasma Cells

PD-L1hi plasmablasts limit the T cell response during the acute phase of parasite infections

Paradoxical sleep deprivation impairs mouse survival after infection with malaria parasites

Contact Info

Product

Resources

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PD-L1^hi plasmablasts limit the T cell response during the acute phase of parasite infections