scholarly journals Vaccination With the Commensal Streptococcus mitis Expressing Pneumococcal Serotype 5 Capsule Elicits IgG/IgA and Th17 Responses Against Streptococcus pneumoniae

2021 ◽  
Vol 12 ◽  
Author(s):  
Sudhanshu Shekhar ◽  
Heidi A. Åmdal ◽  
Fernanda Cristina Petersen
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protective Immunity ◽  
Mediastinal Lymph Node ◽  
Pneumococcal Infection ◽  
Streptococcus Mitis ◽  
Serotype 5 ◽  
Pneumococcal Serotype ◽  
Iga Antibody ◽  
Antibody Levels

Recent studies have identified a clinical isolate of the commensal Streptococcus mitis that expresses Streptococcus pneumoniae serotype 5 capsule (S. mitis serotype 5) and shows serospecificity toward pneumococcal serotype 5. However, it remains unknown whether S. mitis serotype 5 induces protective immunity against pneumococcal serotype 5. In this study, we evaluated the ability of S. mitis serotype 5 to generate protective immunity in a mouse model of lung infection with pneumococcal serotype 5. Upon challenge infection with S. pneumoniae serotype 5, mice intranasally immunized with S. mitis serotype 5 exhibited reduced pneumococcal loads in the lungs, nasal wash, and bronchoalveolar lavage fluid compared with those receiving PBS (control). The immunized mice displayed significantly higher levels of IgG and IgA antibodies reactive to S. mitis serotype 5, S. pneumoniae serotype 5 or S. pneumoniae serotype 4 than the antibody levels in control mice. In vaccinated mice, the IgG/IgA antibody levels reactive to S. mitis serotype 5 or S. pneumoniae serotype 5 were higher than the levels reactive to S. pneumoniae serotype 4. Furthermore, in-vitro restimulation of the lung-draining mediastinal lymph node cells and splenocytes from immunized mice with killed S. mitis serotype 5, S. pneumoniae serotype 5 or S. pneumoniae serotype 4 showed enhanced Th17, but not Th1 and Th2, responses. Overall, our findings show that mucosal immunization with S. mitis serotype 5 protects against S. pneumoniae serotype 5 infection and induces Th17 and predominant serotype-specific IgG/IgA antibody responses against pneumococcal infection.

scholarly journals Absent in melanoma 2 inflammasome is required for host defence against Streptococcus pneumoniae infection

2019 ◽  
Vol 25 (7) ◽  
pp. 412-419 ◽  
Author(s):  
Siwei Feng ◽  
Tingting Chen ◽  
Guihua Lei ◽  
Fengqing Hou ◽  
Jiali Jiang ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Infection ◽  
Host Defence ◽  
Mortality And Morbidity ◽  
Caspase 1 ◽  
Pyrin Domain ◽  
Increased Susceptibility

Streptococcus pneumoniae, a leading cause of invasive pneumococcal disease, is responsible for high mortality and morbidity worldwide. A previous study showed that the NLR family pyrin domain containing 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammasomes are essential for caspase-1 activation and IL-1β production in the host response to S. pneumoniae infection. The function of NLRP3 in host innate immunity to S. pneumoniae was studied in vivo and in vitro. However, the role of AIM2 in host defence against S. pneumoniae remains unclear. Here, we show that AIM2-deficient (AIM2–/–) mice display increased susceptibility to intra-nasal infection with S. pneumoniae in comparison to wild type mice and that this susceptibility was associated with defective IL-1β production. Macrophages from AIM2–/– mice infected with S. pneumoniae showed impaired secretion of IL-1β as well as activation of the inflammasome, as determined by the oligomerisation of apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 activation. Taken together, these results indicate that the AIM2 inflammasome is essential for caspase-1-dependent cytokine IL-1β production and eventual protection from pneumococcal infection in mice.

scholarly journals Interleukin-17A Secreted from the Lung–infiltrating T Helper 17 Cells Renders Protective Immunity to PulmonaryCryptococcus neoformansInfection

2018 ◽  
Author(s):  
Elaheh Movahed ◽  
Grace Min Yi Tan ◽  
Heng Choon Cheong ◽  
Chalystha Yie Qin Lee ◽  
Yi Ying Cheok ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Mediastinal Lymph Node ◽  
Green Fluorescence Protein ◽  
Lavage Fluid ◽  
T Helper 17 ◽  
Protective Function ◽  
Interleukin 17A ◽  
Egfp Reporter

ABSTRACTIL-17A has emerged as a key player in the pathologies of inflammation, autoimmune disease, and immunity to microbes since its discovery two decades ago. In this study, we aim to elucidate the activity of IL-17A in the protection againstCryptococcus neoformans, an opportunistic fungus that causes fatal meningoencephalitis among AIDS patients. For this purpose, we examined ifC. neoformansinfection triggers IL-17A secretion in thein vitrosetting using RAW264.7 murine macrophage cells, andin vivousing wildtype C57BL/6 mice. In addition, an enhanced green fluorescence protein (eGFP) reporter and a knockout (KO) mouse models were used to track the source of IL-17A secretion and explore the protective function of IL-17A, respectively. Our findings showed that bothin vivoandin vitromodels ofC. neoformansinfection demonstrated induction of abundant IL-17A secretion. By examining the lung bronchoalveolar lavage fluid (BALF), mediastinal lymph node (mLN) and spleen of the IL-17A– EGFP reporter mice, we showed that intranasal inoculation withC. neoformanspromoted leukocytes lung infiltration. A large proportion (~50%) of the infiltrated CD4+helper T cell population secreted EGFP, indicating vigorous TH17 activity in theC. neoformans–infected lung. The infection study in IL-17A–KO mice, on the other hand, revealed that absence of IL-17A marginally boosted fungal burden in the lung and accelerated the mouse death. Therefore, our data suggest that IL-17A, released predominantly from TH17 cellsin vivo, is essential in providing a protective immunity againstC. neoformansinfection.

scholarly journals Extracellular adenosine enhances the ability of PMNs to kill Streptococcus pneumoniae by inhibiting IL-10 production

2019 ◽  
Author(s):  
Nalat Siwapornchai ◽  
James N. Lee ◽  
Essi Y. I. Tchalla ◽  
Manmeet Bhalla ◽  
Jun Hui Yeoh ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Infection ◽  
Wild Type ◽  
Extracellular Adenosine ◽  
Phenotypic Differences ◽  
Initial Control ◽  
Bacterial Uptake ◽  
Human Pmns ◽  
Cd73 Expression

AbstractPMNs are crucial for initial control of Streptococcus pneumoniae (pneumococcus) lung infection; however, as the infection progresses their persistence in the lungs becomes detrimental. Here we explored why the anti-microbial efficacy of PMNs declines over the course of infection. We found that the progressive inability of PMNs to control infection correlated with phenotypic differences characterized by a decrease in CD73 expression, an enzyme required for production of extracellular adenosine (EAD). EAD production by CD73 was crucial for the ability of both murine and human PMNs to kill S. pneumoniae. In exploring the mechanisms by which CD73 controlled PMN function, we found that CD73 mediated its anti-microbial activity by inhibiting IL-10 production. PMNs from wild type mice did not increase IL-10 production in response to S. pneumoniae, however, CD73-/- PMNs up-regulated IL-10 production upon pneumococcal infection in vitro and during lung challenge. IL-10 inhibited the ability of wild type PMNs to kill pneumococci. Conversely, blocking IL-10 boosted the bactericidal activity of CD73-/- PMNs as well as host resistance of CD73-/- mice to pneumococcal pneumonia. CD73/IL-10 did not affect apoptosis, bacterial uptake and intracellular killing or production of anti-microbial Neutrophil Elastase and Myeloperoxidase. Rather, inhibition of IL-10 production by CD73 was important for optimal ROS production by PMNs. ROS contributed to PMN anti-microbial function as their removal or detoxification impaired the ability of PMNs to efficiently kill S. pneumoniae. This study demonstrates that CD73 controls PMN anti-microbial phenotype during S. pneumoniae infection.

scholarly journals Intranasal Immunization with the Commensal Streptococcus mitis Confers Protective Immunity against Pneumococcal Lung Infection

2019 ◽  
Vol 85 (6) ◽  
Author(s):  
Sudhanshu Shekhar ◽  
Rabia Khan ◽  
Karl Schenck ◽  
Fernanda Cristina Petersen
Keyword(s):  
Streptococcus Pneumoniae ◽  
Protective Effect ◽  
Protective Immunity ◽  
Lung Infection ◽  
Health Concern ◽  
Pneumococcal Vaccines ◽  
Pneumococcal Serotypes ◽  
Streptococcus Mitis ◽  
Content Type ◽  
Intranasal Immunization

ABSTRACT Streptococcus pneumoniae is a bacterial pathogen that causes various diseases of public health concern worldwide. Current pneumococcal vaccines target the capsular polysaccharide surrounding the cells. However, only up to 13 of more than 90 pneumococcal capsular serotypes are represented in the current conjugate vaccines. In this study, we used two experimental approaches to evaluate the potential of Streptococcus mitis, a commensal that exhibits immune cross-reactivity with S. pneumoniae, to confer protective immunity to S. pneumoniae lung infection in mice. First, we assessed the immune response and protective effect of wild-type S. mitis against lung infection by S. pneumoniae strains D39 (serotype 2) and TIGR4 (serotype 4). Second, we examined the ability of an S. mitis mutant expressing the S. pneumoniae type 4 capsule (S. mitis TIGR4cps) to elicit focused protection against S. pneumoniae TIGR4. Our results showed that intranasal immunization of mice with S. mitis produced significantly higher levels of serum IgG and IgA antibodies reactive to both S. mitis and S. pneumoniae, as well as enhanced production of interleukin 17A (IL-17A), but not gamma interferon (IFN-γ) and IL-4, compared with control mice. The immunization resulted in a reduced bacterial load in respiratory tissues following lung infection with S. pneumoniae TIGR4 or D39 compared with control mice. With S. mitis TIGR4cps, protection upon challenge with S. pneumoniae TIGR4 was superior. Thus, these findings show the potential of S. mitis to elicit natural serotype-independent protection against two pneumococcal serotypes and to provide the benefits of the well-recognized protective effect of capsule-targeting vaccines. IMPORTANCE Streptococcus pneumoniae causes various diseases worldwide. Current pneumococcal vaccines protect against a limited number of more than 90 pneumococcal serotypes, accentuating the urgent need to develop novel prophylactic strategies. S. pneumoniae and the commensal Streptococcus mitis share immunogenic characteristics that make S. mitis an attractive vaccine candidate against S. pneumoniae. In this study, we evaluated the potential of S. mitis and its mutant expressing pneumococcal capsule type 4 (S. mitis TIGR4cps) to induce protection against S. pneumoniae lung infection in mice. Our findings show that intranasal vaccination with S. mitis protects against S. pneumoniae strains D39 (serotype 2) and TIGR4 (serotype 4) in a serotype-independent fashion, which is associated with enhanced antibody and T cell responses. Furthermore, S. mitis TIGR4cps conferred additional protection against S. pneumoniae TIGR4, but not against D39. The findings highlight the potential of S. mitis to generate protection that combines both serotype-independent and serotype-specific responses.

scholarly journals Immunization with PspA Incorporated into a Poly(Ethylene Oxide) Matrix Elicits Protective Immunity against Streptococcus pneumoniae

2007 ◽  
Vol 14 (6) ◽  
pp. 789-791 ◽  
Author(s):  
Quincy C. Moore ◽  
LaShundra Johnson ◽  
Michael Repka ◽  
Larry S. McDaniel
Keyword(s):  
Immune Response ◽  
Streptococcus Pneumoniae ◽  
Ethylene Oxide ◽  
Protective Immunity ◽  
The Matrix ◽  
Poly Ethylene Oxide ◽  
Oxide Matrix ◽  
Poly Ethylene ◽  
Antibody Levels

ABSTRACT CBA/N mice were immunized with PspA in a poly(ethylene oxide) matrix to examine its ability to deliver the antigen and modulate the immune response. All mice receiving PspA in the matrix survived a lethal pneumococcal challenge and had serum anti-PspA antibody levels statistically higher than mice receiving PspA alone (P < 0.009).

scholarly journals Analysis of the In Vitro Transcriptional Response of Human Pharyngeal Epithelial Cells to Adherent Streptococcus pneumoniae: Evidence for a Distinct Response to Encapsulated Strains

2007 ◽  
Vol 75 (11) ◽  
pp. 5489-5499 ◽  
Author(s):  
Hester J. Bootsma ◽  
Michael Egmont-Petersen ◽  
Peter W. M. Hermans
Keyword(s):  
Streptococcus Pneumoniae ◽  
Pneumococcal Infection ◽  
Transcriptional Response ◽  
Innate Immune ◽  
Mitogen Activated Protein Kinase ◽  
Immunity Genes ◽  
Mitogen Activated Protein ◽  
Protein Kinase Signaling ◽  
Host Genes

ABSTRACT Infection of the human host by Streptococcus pneumoniae begins with colonization of the nasopharynx, which is mediated by the adherence of bacteria to the respiratory epithelium. Several studies have indicated an important role for the pneumococcal capsule in this process. Here, we used microarrays to characterize the in vitro transcriptional response of human pharyngeal epithelial Detroit 562 cells to the adherence of serotype 2 encapsulated strain D39, serotype 19F encapsulated strain G54, serotype 4 encapsulated strain TIGR4, and their nonencapsulated derivatives (Δcps). In total, 322 genes were found to be upregulated in response to adherent pneumococci. Twenty-two genes were commonly induced, including those encoding several cytokines (e.g., interleukin 1β [IL-1β] and IL-6), chemokines (e.g., IL-8 and CXCL1/2), and transcriptional regulators (e.g., FOS), consistent with an innate immune response mediated by Toll-like receptor signaling. Interestingly, 85% of genes were induced specifically by one or more encapsulated strains, suggestive of a capsule-dependent response. Importantly, purified capsular polysaccharides alone had no effect. Over a third of these loci encoded products predicted to be involved in transcriptional regulation and signal transduction, in particular mitogen-activated protein kinase signaling pathways. Real-time PCR of a subset of 10 genes confirmed the microarray data and showed a time-dependent upregulation of, especially, innate immunity genes. The downregulation of epithelial genes was most pronounced upon adherence of D39Δcps, as 68% of the 161 genes identified were repressed only by this nonencapsulated strain. In conclusion, we identified a subset of host genes specifically induced by encapsulated strains during in vitro adherence and have demonstrated the complexity of interactions occurring during the initial stages of pneumococcal infection.

scholarly journals A Colanic Acid Operon Deletion Mutation Enhances Induction of Early Antibody Responses by Live Attenuated Salmonella Vaccine Strains

2013 ◽  
Vol 81 (9) ◽  
pp. 3148-3162 ◽  
Author(s):  
Shifeng Wang ◽  
Huoying Shi ◽  
Yuhua Li ◽  
Zhaoxing Shi ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Protective Immunity ◽  
Protective Antigen ◽  
Deletion Mutation ◽  
Antibody Responses ◽  
Content Type ◽  
Colanic Acid ◽  
Iga Antibody ◽  
Ifn Γ

ABSTRACTColanic acid (CA) is a common exopolysaccharide produced by many genera in theEnterobacteriaceae. It is critical for biofilm formation on HEp-2 cells and on chicken intestinal tissue bySalmonella. In this study, we generated different CA synthesis gene mutants and evaluated the immune responses induced by these mutants. One of these mutations, Δ(wza-wcaM)8, which deleted the whole operon for CA synthesis, was introduced into twoSalmonellavaccine strains attenuated by auxotrophic traits or by the regulated delayed attenuation strategy (RDAS). The mice immunized with the auxotrophicSalmonellavaccine strain with the deletion mutation Δ(wza-wcaM)8developed higher vaginal IgA titers against the heterologous protective antigen and higher levels of antigen-specific IgA secretion cells in lungs. InSalmonellavaccine strains with RDAS, the strain with the Δ(wza-wcaM)8mutation resulted in higher levels of protective antigen production duringin vitrogrowth. Mice immunized with this strain developed higher serum IgG and mucosal IgA antibody responses at 2 weeks. This strain also resulted in better gamma interferon (IFN-γ) responses than the strain without this deletion at doses of 108and 109CFU. Thus, the mutation Δ(wza-wcaM)8will be included in various recombinant attenuatedSalmonellavaccine (RASV) strains with RDAS derived fromSalmonella entericaserovar Paratyphi A andSalmonella entericaserovar Typhi to induce protective immunity against bacterial pathogens.

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