scholarly journals A Nonfunctional Opsonic Antibody Response Frequently Occurs after Pneumococcal Pneumonia and Is Associated with Invasive Disease

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Fabian Uddén ◽  
Jonas Ahl ◽  
Nils Littorin ◽  
Kristoffer Strålin ◽  
Simon Athlin ◽  
...  

ABSTRACT Naturally acquired opsonic antipneumococcal antibodies are commonly found in nonvaccinated adults and confer protection against infection and colonization. Despite this, only limited data exist regarding the adaptive immune response after pneumococcal exposure. To investigate the dynamics of naturally acquired antipneumococcal immunity in relation to an episode of infection, opsonic antibody activity was studied with paired acute-phase and convalescent-phase sera obtained from 54 patients with pneumococcal community-acquired pneumonia (CAP) using an opsonophagocytic assay (OPA). Results were compared with clinical characteristics and anticapsular immunoglobulin (Ig) concentrations. Interestingly, a nonfunctional opsonic antibody response (characterized by a decreased convalescent-phase serum OPA titer compared to that of the acute-phase serum or undetectable titers in both sera) was observed in 19 (35%) patients. A nonfunctional convalescent-phase response was significantly more common among patients with invasive pneumococcal disease (i.e., bacteremia) than in patients without invasive disease (53%; P = 0.019). Remaining individuals exhibited either an increased convalescent-phase OPA titer (n = 24 [44%]) or a detectable, but unchanged, titer at both time points (n = 11 [20%]). No correlation was found between anticapsular Ig concentrations and OPA titers. Our findings indicate that an episode of pneumococcal infection may act as an immunizing event, leading to an improved antipneumococcal adaptive immune status. However, in some cases, when patients with CAP also suffer from bacteremia, a nonfunctional opsonic antibody response may occur. Furthermore, the results suggest that factors other than anticapsular Ig concentrations are important for opsonic antibody activity in serum. IMPORTANCE Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response frequently fails to occur after CAP, predominantly among patients with simultaneous bacteremia.


mSphere ◽  
2020 ◽  
Vol 5 (6) ◽  
Author(s):  
Fabian Uddén ◽  
Jonas Ahl ◽  
Nils Littorin ◽  
Kristoffer Strålin ◽  
Simon Athlin ◽  
...  

ABSTRACT Naturally acquired opsonic antipneumococcal antibodies are commonly found in nonvaccinated adults and confer protection against infection and colonization. Despite this, only limited data exist regarding the adaptive immune response after pneumococcal exposure. To investigate the dynamics of naturally acquired antipneumococcal immunity in relation to an episode of infection, opsonic antibody activity was studied with paired acute-phase and convalescent-phase sera obtained from 54 patients with pneumococcal community-acquired pneumonia (CAP) using an opsonophagocytic assay (OPA). Results were compared with clinical characteristics and anticapsular immunoglobulin (Ig) concentrations. Interestingly, a nonfunctional opsonic antibody response (characterized by a decreased convalescent-phase serum OPA titer compared to that of the acute-phase serum or undetectable titers in both sera) was observed in 19 (35%) patients. The remaining individuals exhibited either an increased convalescent-phase OPA titer (n  =  24 [44%]) or a detectable, but unchanged, titer at both time points (n = 11 [20%]). Invasive pneumococcal disease (i.e., bacteremia) was significantly more common among patients with a nonfunctional convalescent-phase response than in patients with other convalescent-phase responses. Anticapsular Ig concentrations were higher among patients with detectable convalescent-phase OPA titers (P = 0.003), and the greatest Ig concentration increase was observed among patients with an increased convalescent-phase response (P = 0.002). Our findings indicate that an episode of pneumococcal infection may act as an immunizing event. However, in some cases when patients with CAP also suffer from bacteremia, a nonfunctional opsonic antibody response may occur. Furthermore, the results suggest that factors other than anticapsular Ig concentrations determine opsonic antibody activity in serum. IMPORTANCE Numerous reports on the dynamics of antipneumococcal immunity in relation to immunization with pneumococcal vaccines and on the prevalence of naturally acquired immunity in various populations have been published. In contrast, studies on the dynamics of the humoral immune response triggered by pneumococcal infection are scarce. This study provides valuable information that will contribute to fill this knowledge gap. Our main results indicate that a functional immune response may fail after CAP, predominantly among patients with simultaneous bacteremia.



2015 ◽  
Vol 153 (5) ◽  
pp. 929-942 ◽  
Author(s):  
A. KIDANE ◽  
I. L. NESHEIM ◽  
H. J. S. LARSEN ◽  
E. THUEN ◽  
S. K. JENSEN ◽  
...  

SUMMARYThe objective of the current experiment was to compare the effects of supplementing mid-lactation dairy cows with all-rac-α-tocopheryl acetate (SyntvE), RRR-α-tocopheryl acetate (NatvE) or seaweed meal (Seaweed) in the presence of a Control group (no supplemental vitamin E or seaweed) on the concentration of α-tocopherol in plasma and milk, and antibody response following immunization. The hypothesis was that supplementation of dairy cows with vitamin E, regardless of its form, would increase plasma and milk α-tocopherol compared to the control diet and this incremental response would be bigger with NatvE than SyntvE. Furthermore, it was hypothesized that vitamin E, regardless of its form, will provide an improved adaptive immune response to immunization than the Control diet, and cows supplemented with Seaweed meal would produce better adaptive immune response following immunization than cows in the Control group. Twenty-four Norwegian Red (NR) dairy cows in their mid-lactation were allocated randomly to the four treatments in a replicated Latin square design. The cows were fed on a basal diet of silage and concentrate on top of which the experimental supplements were provided. Plasma and milk α-tocopherol concentrations were higher in NatvE and SyntvE groups than in the other two groups. The RRR-α-tocopherol stereoisomer was the predominant form (>0·86), in both plasma and milk, whereas the remaining part was largely made up of the other three 2R stereoisomers (RRS, RSR and RSS). In cows fed the Control, Seaweed and NatvE, the proportion of the RRR-α-tocopherol stereoisomer in plasma and milk constituted >0·97 of the total α-tocopherol. Mid-lactation NR dairy cows had higher than adequate levels of plasma α-tocopherol (9·99 mg/l) even when not supplemented with external source of vitamin E, suggesting that with a good quality silage these cows may not be at risk of vitamin E deficiency. Furthermore, the present study shows that dairy cows in mid to late lactation have preferential uptake of RRR stereoisomer of α-tocopherol compared with other stereoisomers. All cows responded well to immunization with different antigens, but there were no significant group effects of the diet on the immune response measured.



2018 ◽  
Vol 92 (16) ◽  
Author(s):  
James M. Burke ◽  
Clovis R. Bass ◽  
Rodney P. Kincaid ◽  
Emin T. Ulug ◽  
Christopher S. Sullivan

ABSTRACTPolyomaviruses (PyVs) can cause serious disease in immunosuppressed hosts. Several pathogenic PyVs encode microRNAs (miRNAs), small RNAs that regulate gene expression via RNA silencing. Despite recent advances in understanding the activities of PyV miRNAs, the biological functions of PyV miRNAs duringin vivoinfections are mostly unknown. The studies presented here used murine polyomavirus (MuPyV) as a model to assess the roles of the PyV miRNAs in a natural host. This analysis revealed that a MuPyV mutant that is unable to express miRNAs has enhanced viral DNA loads in select tissues at late times after infection. This is consistent with the PyV miRNAs functioning to reduce viral replication during the persistent phase of infection in a natural host. Additionally, the MuPyV miRNA locus promotes viruria during the acute phase of infection as evidenced by a defect in shedding during infection with the miRNA mutant virus. The viruria defect of the miRNA mutant virus could be rescued by infectingRag2−/−mice. These findings implicate the miRNA locus as functioning in both the persistent and acute phases of infection and suggest a role for MuPyV miRNA in evading the adaptive immune response.IMPORTANCEMicroRNAs are expressed by diverse viruses, but for only a few is there any understanding of theirin vivofunction. PyVs can cause serious disease in immunocompromised hosts. Therefore, increased knowledge of how these viruses interact with the immune response is of clinical relevance. Here we show a novel activity for a viral miRNA locus in promoting virus shedding. This work indicates that in addition to any role for the PyV miRNA locus in long-term persistence, it also has biological activity during the acute phase. As this mutant phenotype is alleviated by infection of mice lacking an adaptive immune response, our work also connects thein vivoactivity of the PyV miRNA locus to the immune response. Given that PyV-associated disease is associated with alterations in the immune response, our findings help to better understand how the balance between PyVs and the immune response becomes altered in pathogenic states.



2017 ◽  
Author(s):  
James M. Burke ◽  
Clovis R. Bass ◽  
Emin T. Ulug ◽  
Christopher S. Sullivan

AbstractPolyomaviruses (PyVs) can cause serious disease in immunosuppressed hosts. Several pathogenic PyVs encode microRNAs (miRNAs), small RNAs that regulate gene expression via RNA silencing. Despite recent advances in understanding the activities of PyV miRNAs, the biological functions of PyV miRNAs duringin vivoinfections are mostly unknown. Studies presented here use murine polyomavirus (MuPyV) as a model to assess the roles of the PyV miRNAs in a natural host. This analysis reveals that a MuPyV mutant that is unable to express miRNAs has enhanced viral DNA loads in select tissues at late times after infection, indicating that during infection of a natural host, PyV miRNAs function to reduce viral replication during the persistent phase of infection. Additionally, MuPyV miRNAs promote viruria during the acute phase of infection as evidenced by a defect in shedding during infection with the miRNA mutant virus. The viruria defect of the miRNA mutant virus could be rescued by infecting Rag2-/-mice. These findings implicate miRNA activity in both the persistent and acute phases of infection and suggest a role for MuPyV miRNA in evading the adaptive immune response.ImportanceMicroRNAs are expressed by diverse viruses, but for only a few is there any understanding of theirin vivofunction. PyVs can cause serious disease in immunocompromised hosts. Therefore, increased knowledge of how these viruses interact with the immune response is of possible clinical relevance. Here we show a novel activity for a viral miRNA in promoting virus shedding. This work indicates that in addition to any role for the PyV miRNA in long-term persistence, that it also has biological activity during the acute phase. As this mutant phenotype is alleviated by infection of mice lacking an effective adaptive immune response, our work also connects thein vivoactivity of a PyV miRNA to the immune response. Given that PyV-associated disease is associated with alterations in the immune response, our findings may help to better understand how the balance between PyV and the immune response becomes altered in pathogenic states.





2019 ◽  
Vol 80 (12) ◽  
pp. 999-1005 ◽  
Author(s):  
Barbara Misme-Aucouturier ◽  
Adel Touahri ◽  
Marjorie Albassier ◽  
Francine Jotereau ◽  
Patrice Le Pape ◽  
...  


Author(s):  
Alba Grifoni ◽  
John Sidney ◽  
Randi Vita ◽  
Bjoern Peters ◽  
Shane Crotty ◽  
...  


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