scholarly journals Protective Role of Passively Transferred Maternal Cytokines against Bordetella pertussis Infection in Newborn Piglets

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Shokrollah Elahi ◽  
David R. Thompson ◽  
Jill Van Kessel ◽  
Lorne A. Babiuk ◽  
Volker Gerdts

ABSTRACT Maternal vaccination represents a potential strategy to protect both the mother and the offspring against life-threatening infections. This protective role has mainly been associated with antibodies, but the role of cell-mediated immunity, in particular passively transferred cytokines, is not well understood. Here, using a pertussis model, we have demonstrated that immunization of pregnant sows with heat-inactivated bacteria leads to induction of a wide range of cytokines (e.g., tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], interleukin-6 [IL-6], IL-8, and IL-12/IL-23p40) in addition to pertussis-specific antibodies. These cytokines can be detected in the sera and colostrum/milk of vaccinated sows and subsequently were detected at significant levels in the serum and bronchoalveolar lavage fluid of piglets born to vaccinated sows together with pertussis-specific antibodies. In contrast, active vaccination of newborn piglets with heat-inactivated bacteria induced high levels of specific IgG and IgA but no cytokines. Although the levels of antibodies in vaccinated piglets were comparable to those of passively transferred antibodies, no protection against Bordetella pertussis infection was observed. Thus, our results demonstrate that a combination of passively transferred cytokines and antibodies is crucial for disease protection. The presence of passively transferred cytokines/antibodies influences the cytokine secretion ability of splenocytes in the neonate, which provides novel evidence that maternal immunization can influence the newborn's cytokine milieu and may impact immune cell differentiation (e.g., Th1/Th2 phenotype). Therefore, these maternally derived cytokines may play an essential role both as mediators of early defense against infections and possibly as modulators of the immune repertoire of the offspring.

2020 ◽  
Vol 44 (1) ◽  
Author(s):  
Marian Nabil ◽  
Entesar E. Hassan ◽  
Neven S. Ghaly ◽  
Fawzia A. Aly ◽  
Farouk R. Melek ◽  
...  

Abstract Background The genus Albizia (Leguminoseae) is used in folk medicine for the treatment of a wide range of ailments. Recently, saponins from plant origin have attracted much attention. Saponins are recorded to have a broad range of biological and pharmacological activities. This study was performed to evaluate the protective role of Albizia chinensis bark methanolic extract (MEAC) against the genotoxicity induced by cyclophosphamide (CP) using different mutagenic parameters. Results The results showed that MEAC induced an inhibitory effect against chromosomal aberrations of CP in mouse bone marrow and spermatocytes. Such effect was found to be significant (p < 0.01) with a dose of 100 mg/kg treated once for 24 h and also after repeated treatment at a dose of 25 mg/kg for 7 days. In sperm abnormalities, the protective effect of Albizia extract showed a dose-related relationship. Different doses of MEAC (25, 50, and 100 mg/kg) significantly (p < 0.01) ameliorated sperm abnormalities induced by CP dose-dependently. The percentage of sperm abnormalities was decreased to 5.14 ± 0.72 in the group of animals treated with CP plus MEAC (100 mg/kg) indicating an inhibitory effect of about 50%. Conclusion MEAC at the doses examined was non-genotoxic compared to control (negative) and exhibited a protective role against CP genotoxicity.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Iwona Wojcik ◽  
David E. Schmidt ◽  
Lisa A. de Neef ◽  
Minke A. E. Rab ◽  
Bob Meek ◽  
...  

AbstractAs a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.


Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 648
Author(s):  
Tatiana Kotomina ◽  
Irina Isakova-Sivak ◽  
Ki-Hye Kim ◽  
Bo Ryoung Park ◽  
Yu-Jin Jung ◽  
...  

Influenza viruses constantly evolve, reducing the overall protective effect of routine vaccination campaigns. Many different strategies are being explored to design universal influenza vaccines capable of protecting against evolutionary diverged viruses. The ectodomain of influenza A M2e protein (M2e) is among the most promising targets for universal vaccine design. Here, we generated two recombinant live attenuated influenza vaccines (LAIVs) expressing additional four M2e tandem repeats (4M2e) from the N-terminus of the viral hemagglutinin (HA) protein, in an attempt to enhance the M2e-mediated cross-protection. The recombinant H1N1+4M2e and H3N2+4M2e viruses retained growth characteristics attributable to traditional LAIV viruses and induced robust influenza-specific antibody responses in BALB/c mice, although M2e-specific antibodies were raised only after two-dose vaccination with LAIV+4M2e viruses. Mice immunized with either LAIV or LAIV+4M2e viruses were fully protected against a panel of heterologous influenza challenge viruses suggesting that antibody and cell-mediated immunity contributed to the protection. The protective role of the M2e-specific antibody was seen in passive serum transfer experiments, where enhancement in the survival rates between classical LAIV and chimeric H3N2+4M2e LAIV was demonstrated for H3N2 and H5N1 heterologous challenge viruses. Overall, the results of our study suggest that M2e-specific antibodies induced by recombinant LAIV+4M2e in addition to cellular immunity by LAIV play an important role in conferring protection against heterologous viruses.


Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 5 ◽  
Author(s):  
Jae Kyung Lee ◽  
Soo-Jin Oh ◽  
Hosun Park ◽  
Ok Sarah Shin

The placenta is a unique mixed organ, composed of both maternal and fetal tissues, that is formed only during pregnancy and serves as the key physiological and immunological barrier preventing maternal–fetal transmission of pathogens. Several viruses can circumvent this physical barrier and enter the fetal compartment, resulting in miscarriage, preterm birth, and birth defects, including microcephaly. The mechanisms underlying viral strategies to evade the protective role of placenta are poorly understood. Here, we reviewed the role of trophoblasts and Hofbauer cells in the placenta and have highlighted characteristics of vertical and perinatal infections caused by a wide range of viruses. Moreover, we explored current progress and future opportunities in cellular targets, pathogenesis, and underlying biological mechanisms of congenital viral infections, as well as novel research models and tools to study the placenta.


2001 ◽  
Vol 69 (8) ◽  
pp. 4846-4850 ◽  
Author(s):  
Sandra M. M. Hellwig ◽  
Annemiek B. van Spriel ◽  
Joop F. P. Schellekens ◽  
Frits R. Mooi ◽  
Jan G. J. van de Winkel

ABSTRACT Infection with Bordetella pertussis, the causative agent of pertussis (whooping cough) in humans, is followed by the production of antibodies of several isotypes, including immunoglobulin A (IgA). Little is known, however, about the role of IgA in immunity against pertussis. Therefore, we studied targeting ofB. pertussis to the myeloid receptor for IgA, FcαRI (CD89), using either IgA purified from immune sera of pertussis patients or bispecific antibodies directed against B. pertussis and FcαRI (CD89 BsAb). Both IgA and CD89 BsAb facilitated FcαRI-mediated binding, phagocytosis, and bacterial killing by human polymorphonuclear leukocytes (PMNL) and PMNL originating from human FcαRI-transgenic mice. Importantly, FcαRI targeting resulted in enhanced bacterial clearance in lungs of transgenic mice. These data support the capacity of IgA to induce anti-B. pertussis effector functions via the myeloid IgA receptor, FcαRI. Increasing the amount of IgA antibodies induced by pertussis vaccines may result in higher vaccine efficacy.


2016 ◽  
Vol 311 (4) ◽  
pp. R714-R720 ◽  
Author(s):  
Lia E. Taylor ◽  
Jennifer C. Sullivan

Obesity is a potent predictor of cardiovascular disease and associated risk factors, including hypertension. Systemic inflammation has been suggested by a number of studies to be an important link between excess adiposity and hypertension, yet the majority of the studies have been conducted exclusively in males. This is problematic since women represent ∼53% of hypertensive cases and are more likely than men to be obese. There is a growing body of literature supporting a central role for immune cell activation in numerous experimental models of hypertension, and both the sex of the subject and the sex of the T cell have been shown to impact blood pressure (BP) responses to hypertensive stimuli. Moreover, sex steroid hormones play an important role in energy homeostasis, as well as in the regulation of immune responses; estrogen, in particular, has a well-known impact on both cardiovascular and metabolic disorders. Therefore, the purpose of this review is to examine whether sex or sex hormones regulate the role of the immune system in the development of hypertension and related vascular dysfunction in response to metabolic changes and stimuli, including a high-fat diet.


2011 ◽  
Vol 79 (7) ◽  
pp. 2554-2566 ◽  
Author(s):  
Winnie W. S. Kum ◽  
Bernard C. Lo ◽  
Hong B. Yu ◽  
B. Brett Finlay

ABSTRACTTheSalmonellaeffector protein SopB has previously been shown to induce activation of Akt and protect epithelial cells from apoptosisin vitro. To characterize the role of Akt2 in host defense againstSalmonella entericaserovar Typhimurium infection, wild-type (WT) mice and mice lacking Akt2 (Akt2 knockout [KO] mice) were infected using aSalmonellaacute gastroenteritis model. Infected Akt2 KO mice showed a more pronounced morbidity and mortality associated with higher bacterial loads in the intestines and elevated levels of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and MCP-1, in the colons at 1 day postinfection compared to those shown in WT mice. Histopathological assessment and immunohistochemical analysis of cecal sections at 1 day postinfection revealed more severe inflammation and higher levels of neutrophil infiltration in the ceca of Akt2 KO mice. Flow cytometry analysis further confirmed an increase in the recruitment of Gr-1+CD11b+neutrophils and F4/80+CD11b+macrophages in the intestines of infected Akt2 KO mice. Additionally, enhanced levels of annexin V+and terminal transferase dUTP nick end labeling-positive (TUNEL+) apoptotic cells in the intestines of infected Akt2 KO mice were also observed, indicating that Akt2 plays an essential role in protection against apoptosis. Finally, the differences in bacterial loads and cecal inflammation in WT and Akt2 KO mice infected with WTSalmonellawere abolished when these mice were infected with thesopBdeletion mutant, indicating that SopB may play a role in protecting the mice fromSalmonellainfection through the activation of Akt2. These data demonstrate a definitive phenotypic abnormality in the innate response in mice lacking Akt2, underscoring the important protective role of Akt2 inSalmonellainfection.


1998 ◽  
Vol 66 (4) ◽  
pp. 1718-1725 ◽  
Author(s):  
Pascale Gueirard ◽  
Anne Druilhe ◽  
Marina Pretolani ◽  
Nicole Guiso

ABSTRACT Bordetella pertussis induces in vitro apoptosis of murine alveolar macrophages by a mechanism that is dependent on expression of bacterial adenylate cyclase-hemolysin. Using a murine respiratory model, we found in this study that intranasal infection with a parental B. pertussis strain, but not with an isogenic variant deficient in the expression of all toxins and adhesins, induced a marked neutrophil accumulation in the bronchoalveolar lavage fluid and an early decrease in macrophage numbers. These phenomena paralleled a time-dependent rise in the proportion of apoptotic nuclei, as detected by flow cytometry, and of macrophages which had engulfed apoptotic bodies. Apoptotic death of bronchopulmonary cells was observed exclusively following intranasal infection with bacteria reisolated from lungs of infected animals and not with B. pertussis collected after in vitro subculture. Using the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling technique coupled to fluorescence microscopy and morphological analysis, we established that the apoptotic cells in bronchoalveolar lavage fluids were neutrophils and macrophages. Histological analysis of the lung tissues from B. pertussis-infected mice showed increased numbers of apoptotic cells in the alveolar compartments. Cellular accumulation in bronchoalveolar lavage fluids and apoptosis of alveolar macrophages were significantly attenuated in mice infected with a mutant deficient in the expression of adenylate cyclase-hemolysin, indicating a role of this enzyme in these processes.


Author(s):  
E. Krieger ◽  
O. Samodova ◽  
L. Titova

Despite high levels of vaccination coverage, pertussis remains a serious problem. Pertussis cases are registered among infants, adolescents, and adults. Infants younger than three months of age have the highest rate of serious clinical course of pertussis. Transplacental transfer of pertussis-specific antibodies induce protection against infection. The available data on antibody level against pertussis among pregnant women in Russia are fragmentary. To evaluate the humoral immunity to Bordetella pertussis in pregnant women and factors associated with seronegative status we performed cross-sectional study including 388 participants. “SeroPertussis IgG” (Israel) enzyme linked immunosorbent assay test-system was used for quantitative measurement of antibodies to pertussis toxin / hemagglutinin. Binary logistic regression analysis was performed to assess factors associated with seronegative status. The median age of the participants was 30 years. The majority of them (51,3%) did not provide documented vaccination against pertussis. A positive (protective) level of anti-pertussis antibodies (10-50 BU/ml) was revealed in the venous blood of 46,9% of pregnant women. In 25,8% of seropositive women, concentration of specific antibodies was high (> 50 BU/ml). That may indirectly indicate recent Bordetella pertussis infection. More than half of the women surveyed (53,1%) did not have a protective titer of antibodies and were considered susceptible to pertussis. Their children will not receive transplacental immunity to infection. Gestational age was significantly associated with seronegative status. Compared to women tested during the first trimester, participants in their third trimester of pregnancy were more likely to be seronegative to pertussis. The odds of being susceptible increased with increased gestational period (p for linear trend < 0,01). There were no significant differences between the seropositive and seronegative participants with regard to age, gravidity and vaccination status. Pertussis booster vaccinations for preschool children, adolescence and healthcare workers dealing with pregnant women and newborns, as well as cocoon vaccination strategy and vaccination during pregnancy, are required to be implemented to protect infants against pertussis.


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