scholarly journals An infant mouse model of influenza virus transmission demonstrates the role of virus-specific shedding, humoral immunity, and sialidase expression by colonizingStreptococcus pneumoniae

2018 ◽  
Author(s):  
Mila Brum Ortigoza ◽  
Simone Blaser ◽  
M. Ammar Zafar ◽  
Alexandria Hammond ◽  
Jeffrey N. Weiser
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Virus Strain ◽  
Humoral Immunity ◽  
Close Contact ◽  
Disease Spread ◽  
Upper Respiratory Tract ◽  
Infant Mouse ◽  
Primary Model

ABSTRACTThe pandemic potential of influenza A viruses (IAV) depends on the infectivity of the host, transmissibility of the virus, and susceptibility of the recipient. While virus traits supporting IAV transmission have been studied in detail using ferret and guinea pig models, there is limited understanding of host traits determining transmissibility and susceptibility because current animal models of transmission are not sufficiently tractable. Although mice remain the primary model to study IAV immunity and pathogenesis, the efficiency of IAV transmission in adult mice has been inconsistent. Here we describe an infant mouse model which support efficient transmission of IAV. We demonstrate that transmission in this model requires young age, close contact, shedding of virus particles from the upper respiratory tract (URT) of infected pups, the use of a transmissible virus strain, and a susceptible recipient. We characterize shedding as a marker of infectiousness that predicts the efficiency of transmission among different influenza virus strains. We also demonstrate that transmissibility and susceptibility to IAV can be inhibited by humoral immunity via maternal-infant transfer of IAV-specific immunoglobulins, and modifications to the URT milieu, via sialidase activity of colonizingStreptococcus pneumoniae(Spn). Due to its simplicity and efficiency, this model can be used to dissect the host’s contribution to IAV transmission and explore new methods to limit contagion.IMPORTANCEThis study provides insight into the role of the virus strain, age, immunity, and URT flora on IAV shedding and transmission efficiency. Using the infant mouse model, we found that: (a) differences in viral shedding of various IAV strains is dependent on specific hemagglutinin (HA) and/or neuraminidase (NA) proteins; (b) host age plays a key role in the efficiency of IAV transmission; (c) levels of IAV-specific immunoglobulins are necessary to limit infectiousness, transmission, and susceptibility to IAV; and (d) expression of sialidases by colonizing Spn antagonize transmission by limiting the acquisition of IAV in recipient hosts. Our findings highlight the need for strategies that limit IAV shedding, and the importance of understanding the function of the URT bacterial composition in IAV transmission. This work reinforces the significance of a tractable animal model to study both viral and host traits affecting IAV contagion, and its potential for optimizing vaccines and therapeutics that target disease spread.

scholarly journals An Infant Mouse Model of Influenza Virus Transmission Demonstrates the Role of Virus-Specific Shedding, Humoral Immunity, and Sialidase Expression by ColonizingStreptococcus pneumoniae

mBio ◽  
2018 ◽  
Vol 9 (6) ◽  
Author(s):  
Mila Brum Ortigoza ◽  
Simone B. Blaser ◽  
M. Ammar Zafar ◽  
Alexandria J. Hammond ◽  
Jeffrey N. Weiser
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Virus Strain ◽  
Humoral Immunity ◽  
Disease Spread ◽  
Upper Respiratory Tract ◽  
Content Type ◽  
Infant Mouse ◽  
Primary Model

ABSTRACTThe pandemic potential of influenza A viruses (IAV) depends on the infectivity of the host, transmissibility of the virus, and susceptibility of the recipient. While virus traits supporting IAV transmission have been studied in detail using ferret and guinea pig models, there is limited understanding of host traits determining transmissibility and susceptibility because current animal models of transmission are not sufficiently tractable. Although mice remain the primary model to study IAV immunity and pathogenesis, the efficiency of IAV transmission in adult mice has been inconsistent. Here we describe an infant mouse model that supports efficient transmission of IAV. We demonstrate that transmission in this model requires young age, close contact, shedding of virus particles from the upper respiratory tract (URT) of infected pups, the use of a transmissible virus strain, and a susceptible recipient. We characterize shedding as a marker of infectiousness that predicts the efficiency of transmission among different influenza virus strains. We also demonstrate that transmissibility and susceptibility to IAV can be inhibited by humoral immunity via maternal-infant transfer of IAV-specific immunoglobulins and modifications to the URT milieu, via sialidase activity of colonizingStreptococcus pneumoniae. Due to its simplicity and efficiency, this model can be used to dissect the host’s contribution to IAV transmission and explore new methods to limit contagion.IMPORTANCEThis study provides insight into the role of the virus strain, age, immunity, and URT flora on IAV shedding and transmission efficiency. Using the infant mouse model, we found that (i) differences in viral shedding of various IAV strains are dependent on specific hemagglutinin (HA) and/or neuraminidase (NA) proteins, (ii) host age plays a key role in the efficiency of IAV transmission, (iii) levels of IAV-specific immunoglobulins are necessary to limit infectiousness, transmission, and susceptibility to IAV, and (iv) expression of sialidases by colonizingS. pneumoniaeantagonizes transmission by limiting the acquisition of IAV in recipient hosts. Our findings highlight the need for strategies that limit IAV shedding and the importance of understanding the function of the URT bacterial composition in IAV transmission. This work reinforces the significance of a tractable animal model to study both viral and host traits affecting IAV contagion and its potential for optimizing vaccines and therapeutics that target disease spread.

scholarly journals Streptococcus pneumoniae Transmission Is Blocked by Type-Specific Immunity in an Infant Mouse Model

mBio ◽  
2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Tonia Zangari ◽  
Yang Wang ◽  
Jeffrey N. Weiser
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mouse Model ◽  
Pneumococcal Conjugate Vaccine ◽  
Herd Immunity ◽  
Mechanistic Explanation ◽  
Epidemiological Studies ◽  
Contributing Factors ◽  
Infant Mouse ◽  
Major Benefit

ABSTRACT Epidemiological studies on Streptococcus pneumoniae show that rates of carriage are highest in early childhood and that the major benefit of the pneumococcal conjugate vaccine (PCV) is a reduction in the incidence of nasopharyngeal colonization through decreased transmission within a population. In this study, we sought to understand how anti- S. pneumoniae immunity affects nasal shedding of bacteria, the limiting step in experimental pneumococcal transmission. Using an infant mouse model, we examined the role of immunity (passed from mother to pup) on shedding and within-litter transmission of S. pneumoniae by pups infected at 4 days of life. Pups from both previously colonized immune and PCV-vaccinated mothers had higher levels of anti- S. pneumoniae IgG than pups from non-immune or non-vaccinated mothers and shed significantly fewer S. pneumoniae over the first 5 days of infection. By setting up cross-foster experiments, we demonstrated that maternal passage of antibody to pups either in utero or post-natally decreases S. pneumoniae shedding. Passive immunization experiments showed that type-specific antibody to capsular polysaccharide is sufficient to decrease shedding and that the agglutinating function of immunoglobulin is required for this effect. Finally, we established that anti-pneumococcal immunity and anti-PCV vaccination block host-to-host transmission of S. pneumoniae . Moreover, immunity in either the donor or recipient pups alone was sufficient to reduce rates of transmission, indicating that decreased shedding and protection from acquisition of colonization are both contributing factors. Our findings provide a mechanistic explanation for the reduced levels of S. pneumoniae transmission between hosts immune from prior exposure and among vaccinated children. IMPORTANCE Rates of carriage of the bacterial pathogen Streptococcus pneumoniae are highest among young children, and this is the target group for the pneumococcal conjugate vaccine (PCV). Epidemiological studies have suggested that a major benefit of the PCV is a reduction in host-to-host transmission, which also protects the non-vaccinated population (“herd immunity”). In this study, we examined the role of anti-pneumococcal immunity on nasal shedding and transmission of the pathogen using an infant mouse model. We found that shedding is decreased and transmission is blocked by anti-pneumococcal immunity and PCV vaccination. Additionally, transmission rates decreased if either the infected or contact pups were immune, indicating that reduced shedding and protection from the establishment of colonization are both contributing factors. Our study provides a mechanistic explanation for the herd immunity effect seen after the introduction of PCV and identifies potential points of intervention, which may have implications for future vaccine development.

scholarly journals Candida-Specific Antibodies during Experimental Vaginal Candidiasis in Mice

2002 ◽  
Vol 70 (10) ◽  
pp. 5790-5799 ◽  
Author(s):  
Karen L. Wozniak ◽  
Floyd L. Wormley ◽  
Paul L. Fidel
Keyword(s):  
Mouse Model ◽  
Host Defense ◽  
Humoral Immunity ◽  
Secondary Infection ◽  
Lavage Fluid ◽  
Protective Role ◽  
Vaginal Candidiasis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specific Antibodies

ABSTRACT Protective host defense mechanisms against vaginal Candida albicans infections are poorly understood. Although cell-mediated immunity (CMI) is the predominant host defense mechanism against most mucosal Candida infections, the role of CMI against vaginal candidiasis is uncertain, both in humans and in an experimental mouse model. The role of humoral immunity is equally unclear. While clinical observations suggest a minimal role for antibodies against vaginal candidiasis, an experimental rat model has provided evidence for a protective role for Candida-specific immunoglobulin A (IgA) antibodies. Additionally, Candida vaccination-induced IgM and IgG3 antibodies are protective in a mouse model of vaginitis. In the present study, the role of infection-induced humoral immunity in protection against experimental vaginal candidiasis was evaluated through the quantification of Candida-specific IgA, IgG, and IgM antibodies in serum and vaginal lavage fluids of mice with primary and secondary (partially protected) infection. In naïve mice, total, but not Candida-specific, antibodies were detected in serum and lavage fluids, consistent with lack of yeast colonization in mice. In infected mice, Candida-specific IgA and IgG antibodies were induced in serum with anamnestic responses to secondary infection. In lavage fluid, while Candida-specific antibodies were detectable, concentrations were extremely low with no anamnestic responses in mice with secondary infection. The incorporation of alternative protocols—including infections in a different strain of mice, prolongation of primary infection prior to secondary challenge, use of different enzyme-linked immunosorbent assay capture antigens, and concentration of lavage fluid—did not enhance local Candida-specific antibody production or detection. Additionally, antibodies were not removed from lavage fluids by being bound to Candida during infection. Together, these data suggest that antibodies are not readily present in vaginal secretions of infected mice and thus have a limited natural protective role against infection.

scholarly journals Historical Discoveries on Viruses in the Environment and Their Impact on Public Health

Intervirology ◽  
2020 ◽  
Vol 63 (1-6) ◽  
pp. 17-32
Author(s):  
Thomas Labadie ◽  
Christophe Batéjat ◽  
India Leclercq ◽  
Jean-Claude Manuguerra
Keyword(s):  
Public Health ◽  
Influenza Virus ◽  
Ebola Virus ◽  
Close Contact ◽  
Abiotic Factors ◽  
Virus Transmission ◽  
Human Coronavirus ◽  
Indirect Transmission ◽  
Droplet Sizes

<b><i>Background:</i></b> Transmission of many viruses occurs by direct transmission during a close contact between two hosts, or by an indirect transmission through the environment. Several and often interconnected factors, both abiotic and biotic, determine the persistence of these viruses released in the environment, which can last from a few seconds to several years. Moreover, viruses in the environment are able to travel short to very long distances, especially in the air or in water. <b><i>Summary:</i></b> Although well described now, the role of these environments as intermediaries or as reservoirs in virus transmission has been extensively studied and debated in the last century. The majority of these discoveries, such as the pioneer work on bacteria transmission, the progressive discoveries of viruses, as well as the persistence of the influenza virus in the air varying along with droplet sizes, or the role of water in the transmission of poliovirus, have contributed to the improvement of public health. Recent outbreaks of human coronavirus, influenza virus, and Ebola virus have also demonstrated the contemporaneity of these research studies and the need to study virus persistence in the environment. <b><i>Key Messages:</i></b> In this review, we discuss historical discoveries that contributed to describe biotic and abiotic factors determining viral persistence in the environment.

scholarly journals Capsule Type and Amount Affect Shedding and Transmission of Streptococcus pneumoniae

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
M. Ammar Zafar ◽  
Shigeto Hamaguchi ◽  
Tonia Zangari ◽  
Michael Cammer ◽  
Jeffrey N. Weiser
Keyword(s):  
Streptococcus Pneumoniae ◽  
Mouse Model ◽  
Human Population ◽  
Capsular Polysaccharide ◽  
Upper Respiratory Tract ◽  
Wild Type ◽  
Infant Mouse ◽  
Capsule Type ◽  
Upper Respiratory ◽  
Epidemiology Studies

ABSTRACT The capsular polysaccharide (CPS) of Streptococcus pneumoniae is characterized by its diversity, as it has over 95 known serotypes, and the variation in its thickness as it surrounds an organism. While within-host effects of CPS have been studied in detail, there is no information about its contribution to host-to-host transmission. In this study, we used an infant mouse model of intralitter transmission, together with isogenic capsule switch and cps promoter switch constructs, to explore the effects of CPS type and amount. The determining factor in the transmission rate in this model is the number of pneumococci shed in nasal secretions by colonized hosts. Two of seven capsule switch constructs showed reduced shedding. These constructs were unimpaired in colonization and expressed capsules similar in size to those of the wild-type strain. A cps promoter switch mutant expressing ~50% of wild-type amounts of CPS also displayed reduced shedding without a defect in colonization. Since shedding from the mucosal surface may require escape from mucus entrapment, a mucin-binding assay was used to compare capsule switch and cps promoter switch mutants. The CPS type or amount constructs that shed poorly were bound more robustly by immobilized mucin. These capsule switch and cps promoter switch constructs with increased mucin-binding affinity and reduced shedding also had lower rates of pup-to-pup transmission. Our results demonstrate that CPS type and amount affect transmission dynamics and may contribute to the marked differences in prevalence among pneumococcal types. IMPORTANCE Streptococcus pneumoniae, a leading cause of morbidity and mortality, is readily transmitted, especially among young children. Its structurally and antigenically diverse capsular polysaccharide is the target of currently licensed pneumococcal vaccines. Epidemiology studies show that only a subset of the >95 distinct serotypes are prevalent in the human population, suggesting that certain capsular polysaccharide types might be more likely to be transmitted within the community. Herein, we used an infant mouse model to show that both capsule type and amount are important determinants in the spread of pneumococci from host to host. Transmission rates correlate with those capsule types that are better at escaping mucus entrapment, a key step in exiting the host upper respiratory tract. Hence, our study provides a better mechanistic understanding of why certain pneumococcal serotypes are more common in the human population. IMPORTANCE Streptococcus pneumoniae, a leading cause of morbidity and mortality, is readily transmitted, especially among young children. Its structurally and antigenically diverse capsular polysaccharide is the target of currently licensed pneumococcal vaccines. Epidemiology studies show that only a subset of the >95 distinct serotypes are prevalent in the human population, suggesting that certain capsular polysaccharide types might be more likely to be transmitted within the community. Herein, we used an infant mouse model to show that both capsule type and amount are important determinants in the spread of pneumococci from host to host. Transmission rates correlate with those capsule types that are better at escaping mucus entrapment, a key step in exiting the host upper respiratory tract. Hence, our study provides a better mechanistic understanding of why certain pneumococcal serotypes are more common in the human population.

Ability of Antibiotic-Resistant Nonvaccine-Type Pneumococcal Clones to Cause Otitis Media in an Infant Mouse Model of Pneumococcal–Influenza Virus Coinfection

2016 ◽  
Vol 22 (1) ◽  
pp. 97-101 ◽  
Author(s):  
Nelson Frazão ◽  
Peter Hermans ◽  
Saskia van Selm ◽  
Raquel Sá-Leão ◽  
Hermínia de Lencastre ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Otitis Media ◽  
Antibiotic Resistant ◽  
Infant Mouse

scholarly journals Three-step Anti-aMPV IgA Expression Profile Evaluation in Turkeys of Different Immunological Status after TRT Vaccination

2016 ◽  
Vol 19 (3) ◽  
pp. 509-518 ◽  
Author(s):  
M. Śmiałek ◽  
B. Tykałowski ◽  
D. Pestka ◽  
J. Welenc ◽  
T. Stenzel ◽  
...  
Keyword(s):  
B Lymphocytes ◽  
Humoral Immunity ◽  
Upper Respiratory Tract ◽  
Antigen Specificity ◽  
Avian Metapneumovirus ◽  
Immunological Status ◽  
Upper Respiratory ◽  
The Impact ◽  
Different Levels

Abstract Maternally derived antibodies (MDA) don not protect turkeys against rhinotracheitis (TRT) but high MDA influences upper respiratory tract (URT) immunity stimulation after avian Metapneumovirus (aMPV) vaccination. Humoral immunity can not be considered as an indicator of protection against TRT, but specific antibodies inhibit aMPV replication and alleviate the course of TRT. Scarce reports indicate the role of IgA in protection against TRT. The aim of our study was to investigate the impact of MDA on stimulation, antigen specificity acquisition of B lymphocytes, and the production of specific IgA after TRT vaccination of turkeys. The results of our study indicate that MDA on the day of TRT vaccination causes disturbances at different levels of specific humoral immunity expression including antigen specificity acquisition of B IgA+ lymphocytes as well as production and secretion of IgA. Vaccine immunity against aMPV associated with sIgA is well expressed in birds not possessing MDA on the day of TRT vaccination, whereas it is inhibited in MDA+ birds. These results corroborate our previous findings and indicate that MDA could be responsible for TRT vaccination failure. These findings could explain the observed frequency of TRT field outbreaks despite aMPV vaccination of turkey flocks.

scholarly journals Exposure to Cigarette Smoke Enhances Pneumococcal Transmission Among Littermates in an Infant Mouse Model

2021 ◽  
Vol 11 ◽  
Author(s):  
Daichi Murakami ◽  
Masamitsu Kono ◽  
Denisa Nanushaj ◽  
Fumie Kaneko ◽  
Tonia Zangari ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Mouse Model ◽  
Cigarette Smoke ◽  
Close Contact ◽  
Smoke Exposure ◽  
Mucosal Barrier ◽  
Cigarette Smoke Exposure ◽  
New Host ◽  
Infant Mouse ◽  
The Impact

Streptococcus pneumoniae, one of the most common commensal pathogens among children, is spread by close contact in daycare centers or within a family. Host innate immune responses and bacterial virulence factors promote pneumococcal transmission. However, investigations into the effects of environmental factors on transmission have been limited. Passive smoking, a great concern for children’s health, has been reported to exacerbate pneumococcal diseases. Here, we describe the effect of cigarette smoke exposure on an infant mouse model of pneumococcal transmission. Our findings reveal that the effect of cigarette smoke exposure significantly promotes pneumococcal transmission by enhancing bacterial shedding from the colonized host and by increasing susceptibility to pneumococcal colonization in the new host, both of which are critical steps of transmission. Local inflammation, followed by mucosal changes (such as mucus hypersecretion and disruption of the mucosal barrier), are important underlying mechanisms for promotion of transmission by smoke exposure. These effects were attributable to the constituents of cigarette smoke rather than smoke itself. These findings provide the first experimental evidence of the impact of environmental factors on pneumococcal transmission and the mechanism of pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document