Respiratory Diseases In Animals Research Articles

Nipah virus: epidemiology, pathogenesis, treatment, and prevention.

Nipah virus (NiV) is a zoonotic paramyxovirus that has recently emerged as a crucial public health issue. It can elicit severe encephalitis and respiratory diseases in animals and humans, leading to fatal outcomes, exhibiting a wide range of host species tropism, and directly transmitting from animals to humans or through an intermediate host. Human-to-human transmission associated with recurrent NiV outbreaks is a potential global health threat. Currently, the lack of effective therapeutics or licensed vaccines for NiV necessitates the primary utilization of supportive care. In this review, we summarize current knowledge of the various aspects of the NiV, including therapeutics, vaccines, and its biological characteristics, epidemiology, pathogenesis, and clinical features. The objective is to provide valuable information from scientific and clinical research and facilitate the formulation of strategies for preventing and controlling the NiV.

Transcriptional dynamics during Rhodococcus erythropolis infection with phage WC1.

Belonging to the Actinobacteria phylum, members of the Rhodococcus genus thrive in soil, water, and even intracellularly. While most species are non-pathogenic, several cause respiratory disease in animals and, more rarely, in humans. Over 100 phages that infect Rhodococcus species have been isolated but despite their importance for Rhodococcus ecology and biotechnology applications, little is known regarding the molecular genetic interactions between phage and host during infection. To address this need, we report RNA-Seq analysis of a novel Rhodococcus erythopolis phage, WC1, analyzing both the phage and host transcriptome at various stages throughout the infection process. By five minutes post-infection WC1 showed upregulation of a CAS-4 family exonuclease, putative immunity repressor, an anti-restriction protein, while the host showed strong upregulation of DNA replication, SOS repair, and ribosomal protein genes. By 30min post-infection, WC1 DNA synthesis genes were strongly upregulated while the host showed increased expression of transcriptional and translational machinery and downregulation of genes involved in carbon, energy, and lipid metabolism pathways. By 60min WC1 strongly upregulated structural genes while the host showed a dramatic disruption of metal ion homeostasis. There was significant expression of both host and phage non-coding genes at all time points. While host gene expression declined over the course of infection, our results indicate that phage may exert more selective control, preserving the host's regulatory mechanisms to create an environment conducive for virion production. The Rhodococcus genus is well recognized for its ability to synthesize valuable compounds, particularly steroids, as well as its capacity to degrade a wide range of harmful environmental pollutants. A detailed understanding of these phage-host interactions and gene expression is not only essential for understanding the ecology of this important genus, but will also facilitate development of phage-mediated strategies for bioremediation as well as biocontrol in industrial processes and biomedical applications. Given the current lack of detailed global gene expression studies on any Rhodococcus species, our study addresses a pressing need to identify tools and genes, such as F6 and rpf, that can enhance the capacity of Rhodococcus species for bioremediation, biosynthesis and pathogen control.

Occurrence in sick animals and genetic heterogeneity of Siberian isolates of bovine respiratory syncytial virus (Pneumoviridae: <i>Orthopneumovirus</i>; BRSV) identified in the territories of the Ural, Siberian Federal District and the Republic of Kazakhstan

Introduction. Bovine respiratory syncytial virus (Pneumoviridae: Orthornavirae, Orthopneumovirus; Bovine orthopneumovirus, Bovine respiratory syncytial virus, BRSV) is one of causative agents of respiratory diseases in animals. The study of the occurrence and genetic diversity of this pathogen is of particular importance.
 Objective. To study the frequency of virus in animals using RT-PCR and genetic heterogeneity of isolates based on determining the complete nucleotide sequence of glycoprotein G gene.
 Materials and methods. A 381-bp region of glycoprotein F gene was used for identification of virus genome, while complete nucleotide sequences of G gene were used for phylogenetic analysis. Phylogenetic trees were constructed using the maximum likelihood method in MEGA 7.0 software.
 Results. During outbreaks of respiratory diseases, BRSV RNA was detected in animals of all ages in samples of lungs, nasal secretions, pulmonary lymph nodes. Complete nucleotide sequences of glycoprotein G gene, 771 bp in length were obtained for five isolates and 789 bp in length ‒ for two isolates. Nucleotide similarity between them was 87–100%. Phylogenetic analysis assigned the isolates to subgroups II and III, each of which included two isolates. A separate clade formed by K18 isolate from animals imported from Canada and sequences from vaccines containing the attenuated «375» strain.
 Conclusion. The virus genome was identified in cows and heifers (20.0 and 14.3%), in calves up 1 month of age (3.05%), and in calves from 1 to 6 months of age (6.7%). Complete G gene nucleotide sequence analysis is a useful tool for studying the molecular epidemiology of BRSV on particular territories.

Prevalence Estimation and Genetic Characterization of Porcine Parainfluenza Virus 1 (PPIV-1) in Hungary and the First Report of the Virus in Slovakia

In the last few decades, many new paramyxoviruses have been discovered, causing diverse, mostly respiratory diseases in animals and humans. The porcine parainfluenza virus 1 (PPIV-1, species Porcine respirovirus 1), which has been reported in many countries worldwide, was found in both healthy and clinically ill pigs showing respiratory signs. Here, we report the expected prevalence and genetic diversity of PPIV-1 in Hungarian pig herds and the detection in one Slovakian pig farm, which is the first report of evidence for the presence of the virus in the country. To estimate the prevalence in Hungary 211 oral fluid samples were collected from 23 large-scale swine herds in a systematic way and tested by real-time quantitative RT-PCR. The presence of the virus was detected in 10 of the 23 Hungarian farms (43%) included in our study. One hundred eighty-one nasal swab samples were collected cross-sectionally from three Hungarian and one Slovakian PPIV-1-positive herd and PPIV-1 was most prevalent in 6-week-old pigs on farms located in Hungary and in the 2-week-old pigs on the Slovakian farm. Phylogenetic analysis of three Hungarian and two Slovakian PPIV-1 F-gene sequences showed high-nucleotide identity (>93%) and all belonged to Clade I, together with the other European strains.

Effect of refloated soil dust on oxidative stress and apoptosis in rat lung

Little study has illustrated the associations between inhalation of refloated soil dust and the morbidity of respiratory disease in animals. In this study, soil dust samples in arid and semiarid areas of China were collected for investigating the underlying biotoxicity and mechanisms of oxidative stress and apoptosis in rat lung induced by inhalation of refloated soil dust. The soil dust samples were collected from the arid and semiarid areas in Zhangjiakou city, located close to Inner Mongolia Plateau, China. After intratracheal instillation of soil dust, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities in rat lung were declined in a dose-dependent relationship, and pathology changes in lung tissue were also enhanced along with increased levels of soil dust. Meanwhile, apoptotic cells were scattered in the pulmonary epithelial and distributed in the mesenchyma, and the apoptotic index was significantly increased in rat lung instilled by soil dust. Besides, soil dust promoted Bax expression and inhibited Bcl2 expression, i.e., increased Bax/Bcl2 ratio in a concentration-dependent manner. In summary, short-term exposure to soil dust caused oxidative damage and induced apoptosis in rat lung through the regulation of Bax and Bcl2 expression.

PM2.5 Synergizes With Pseudomonas aeruginosa to Suppress Alveolar Macrophage Function in Mice Through the mTOR Pathway.

High concentrations of PM2.5 in enclosed broiler houses cause respiratory disorders in humans and animals. Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that can induce severe respiratory disease in animals under stress or with abnormal immune functions. Alveolar macrophages are lung-resident immune cells that play important roles in lung host defence and immune balance. In this study, the mechanism by which PM2.5 synergizes with P. aeruginosa to damage alveolar macrophage function and induce inflammation was investigated. The results will provide a theoretical basis for improving the poultry breeding environment and preventing the recurrence of infection with P. aeruginosa. Alveolar macrophages were stimulated by PM2.5 collected in an enclosed broiler house and P. aeruginosa. Phagocytosis was determined by the neutral red test. The apoptosis rate and cytoskeleton changes were observed by flow cytometry assays and laser scanning confocal microscopy. Protein levels related to autophagy and the mTOR pathway were detected by Western blotting. The results indicated that PM2.5 in combination with P. aeruginosa could decrease phagocytosis, inhibit autophagy, increase apoptosis, and destroy the cytoskeleton in alveolar macrophages. In addition, alveolar macrophages had significantly increased expression of mTOR pathway-related proteins in response to the synergistic stimulation of PM2.5 and P. aeruginosa. The above results confirmed that PM2.5 in poultry houses synergized with P. aeruginosa to impede alveolar macrophage function and caused more severe respiratory system injuries through a process closely related to the activation of the mTOR signalling pathway.

Comparision of biological and genomic characteristics of five virulent bacteriophages against Enterobacter hormaechei

Enterobacter hormaechei is a zoonotic bacteria that may cause respiratory diseases in animals and neonatal sepsis in humans. Bacteriophages are increasingly considered as potential biocontrol agents to control pathogens in the food industry. In this study, five E. hormaechei virulent phages, named as Ehp-YZU08, Ehp-YZU10, Ehp-YZU9-1, Ehp-YZU9-2 and Ehp-YZU9-3, were isolated from sewage in China and analyzed for their biological and whole-genome characteristics, and a comparative genomic analysis was performed to study the functional genes and phylogenetic evolution of phages. The results showed that four of the phage strains belong to the Podoviridae family and one belongs to the Myoviridae family. The burst sizes were 70–283 PFU/cell after a latent period of 5–40 min. Phages were able to survive in a pH range of 5–10 and resist temperatures up to 60 °C for 60 min. The sequencing results showed that the full length of the genomes of the five phages ranged from 39,502 to 173,418 bp. Each phage contained multiple genes related to phage replication, and genes related to bacterial virulence or drug resistance were not found. The five phages belonged to three different groups by a construction of a phylogenetic tree, and the significant genetic evolutionary distance from each E. hormaechei phage was observed. The inhibition assay showed that all five phages could completely inhibit the growth of E. hormaechei at 37 °C within 8 h, suggesting that the phages in this study have great potential for the development of biocontrol agents against E. hormaechei in the food industry.

Isolation and genomic characterization of P.A-5, a novel virulent bacteriophage against Enterobacter hormaechei

Enterobacter hormaechei is a foodborne pathogen responsible for neonatal sepsis in humans and respiratory disease in animals. In this work, a new virulent phage (P.A-5) infecting E. hormaechei was isolated from domestic sewage samples and characterized. Transmission electron microscopy revealed that P.A-5 belonged to the family Myoviridae having a head size of 77.53 nm and a tail length of 72.24 nm. The burst size was 262 PFU/cell after a latent period of 20 min. Phage P.A-5 was able to survive in a pH range of 4–9 and resist temperatures up to 55 °C for 60 min. The genome sequence of P.A-5 had homology most similar to that of Shigellae phage MK-13 (GenBank: MK509462.1). Pork artificially contaminated with E. hormaechei was used as a model to evaluate the potential of P.A-5. The results clearly showed that P.A-5 treatment can completely inhibit E. hormaechei growth in pork within 8 h, indicating the potential use of P.A-5 as a biocontrol agent for E. hormaechei.

Two stage, nested isothermal amplification in a single tube.

Sensitive, specific and rapid molecular diagnosis of respiratory diseases in animals and humans is critical to facilitate appropriate control measures and treatment. Conventional polymerase chain reaction (PCR)-based molecular diagnostics requires relatively expensive equipment and trained staff, restricting its use to centralized laboratories with significant delays between sample collection and test results. Herein, we report a highly sensitive, rapid, point-of-need, two-stage-molecular test that requires minimal instrumentation and training. Our test, dubbed Penn-RAMP, combines recombinase polymerase amplification (RPA, 38 °C) and loop-mediated isothermal amplification (LAMP, 63 °C) in one tube, enabling nested, two-stage isothermal amplification. We demonstrate Penn-RAMP's efficacy by testing for two common viral respiratory diseases of chickens: infectious laryngotracheitis (ILT) and infectious bronchitis (IB) that impose great economic burden worldwide. Test results of clinical samples with our closed-tube Penn-RAMP assays concord with the gold standard quantitative PCR (qPCR) assay; with 10-fold better limit of detection than LAMP and qPCR. Our closed-tube Penn-RAMP assays have the potential to greatly reduce false negatives while requiring minimal instrumentation and training.

A Review of Recent Trend of COVID-19 Infection and Correlation with Pulmonary Function

Coronavirus is generally known to cause minor respiratory diseases in animals and humans. However, some coronavirus genus is reported to cause animal-to-human interspecies infection. Since the end of 2019, a new type of coronavirus (COVID-19) infection is spreading rapidly throughout the world, leading to the declaration of the pandemic by the World Health Organization (WHO). Despite various clinical studies to counter COVID-19 infection, the total confirmed cases and death rates are still accumulating. To break down this new threat, we should pay attention to newly revealed information based on scientific facts. In this review, we introduced the clinical characteristics, diagnostic methods, and treatment of patients infected with COVID-19. Moreover, we highlighted the correlation between COVID-19 severity and patients with underlying diseases. Potential risks associated with COVID-19 can be differed depending on the condition of patients and can cause pulmonary complications. Therefore, lung capacity exams are expected to help predict the progression of the disease along with previously established detection methods such as molecular diagnostics and immunoassay. Although physiological research hasnt yet been emphasized to evaluate COVID-19 infection, this review is expected to be valuable to give new inspiration to deal with COVID-19 which might strike again in the future.

Lithium as a candidate treatment for COVID-19: Promises and pitfalls.

The pandemic of respiratory illness caused by a novel coronavirus (SARS‐nCoV‐2) is a global health crisis. Despite numerous preliminary results, there is as yet no treatment of proven efficacy for this condition. In this context, the pharmacological properties of lithium, better known as a treatment for mood disorders, merit closer examination. Lithium has shown in vitro efficacy at inhibiting the replication of coronaviruses responsible for gastrointestinal and respiratory diseases in animals. It has immunomodulatory properties that may be of additional benefit in moderating the host inflammatory response to the novel coronavirus (SARS‐CoV‐2). Furthermore, there is evidence that lithium may exert a protective action against upper respiratory infections and influenza‐like illnesses in patients taking it for other indications. These promising reports must be balanced against the narrow therapeutic index and high risk of toxicity associated with lithium therapy, its documented interactions with several commonly used drugs, and the absence of evidence of its efficacy against coronaviruses responsible for human disease. Nevertheless, naturalistic studies of the risk of COVID‐19 in patients already receiving lithium could provide indirect evidence of its efficacy, and understanding the putative antiviral and immune‐regulatory mechanisms of lithium in models of SARS‐CoV‐2 infection may provide leads for the development of safer and more effective treatments with a specific action against COVID‐19.

PM2.5 in poultry houses synergizes with Pseudomonas aeruginosa to aggravate lung inflammation in mice through the NF-κB pathway.

BackgroundHigh concentrations of particulate matter less than 2.5 µm in diameter (PM2.5) in poultry houses is an important cause of respiratory disease in animals and humans. Pseudomonas aeruginosa is an opportunistic pathogen that can induce severe respiratory disease in animals under stress or with abnormal immune functions. When excessively high concentrations of PM2.5 in poultry houses damage the respiratory system and impair host immunity, secondary infections with P. aeruginosa can occur and produce a more intense inflammatory response, resulting in more severe lung injury.ObjectivesIn this study, we focused on the synergistic induction of inflammatory injury in the respiratory system and the related molecular mechanisms induced by PM2.5 and P. aeruginosa in poultry houses.MethodsHigh-throughput 16S rDNA sequence analysis was used for characterizing the bacterial diversity and relative abundance of the PM2.5 samples, and the effects of PM2.5 and P. aeruginosa stimulation on inflammation were detected by in vitro and in vivo.ResultsSequencing results indicated that the PM2.5 in poultry houses contained a high abundance of potentially pathogenic genera, such as Pseudomonas (2.94%). The lung tissues of mice had more significant pathological damage when co-stimulated by PM2.5 and P. aeruginosa, and it can increase the expression levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-α through nuclear factor (NF)-κB pathway in vivo and in vitro.ConclusionsThe results confirmed that poultry house PM2.5 in combination with P. aeruginosa could aggravate the inflammatory response and cause more severe respiratory system injuries through a process closely related to the activation of the NF-κB pathway.

Bordetella Colonization Factor A (BcfA) Elicits Protective Immunity against Bordetella bronchiseptica in the Absence of an Additional Adjuvant.

Bordetella bronchiseptica is an etiologic agent of respiratory diseases in animals and humans. Despite the widespread use of veterinary B. bronchiseptica vaccines, there is limited information on their composition and relative efficacy and on the immune responses that they elicit. Furthermore, human B. bronchiseptica vaccines are not available. We leveraged the dual antigenic and adjuvant functions of Bordetella colonization factor A (BcfA) to develop acellular B. bronchiseptica vaccines in the absence of an additional adjuvant. BALB/c mice immunized with BcfA alone or a trivalent vaccine containing BcfA and the Bordetella antigens FHA and Prn were equally protected against challenge with a prototype B. bronchiseptica strain. The trivalent vaccine protected mice significantly better than the canine vaccine Bronchicine and provided protection against a B. bronchiseptica strain isolated from a dog with kennel cough. Th1/17-polarized immune responses correlate with long-lasting protection against bordetellae and other respiratory pathogens. Notably, BcfA strongly attenuated the Th2 responses elicited by FHA and Prn, resulting in Th1/17-skewed responses in inherently Th2-skewed BALB/c mice. Thus, BcfA functions as both an antigen and an adjuvant, providing protection as a single-component vaccine. BcfA-adjuvanted vaccines may improve the efficacy and durability of vaccines against bordetellae and other pathogens.

Role of the microbiome in respiratory disease

"Microbiome” is a term used to describe the community of microorganisms that live on and within vertebrate hosts. These microorganisms primarily live in the gastrointestinal tract and play an important role in nutrient digestion and development of immunity. Understanding the role of the gut microbiome in health and disease is a new and exciting field of study. For decades, the focus on managing infectious disease has been on the pathogen(s) of interest, virtually ignoring the role of beneficial microbes in potentiating or eliminating disease. In addition, initial research evaluating the role of the microbiome in disease was centered on enteric pathogens, due to the inherent proximity of pathogenic and nonpathogenic microorganisms in the digestive tract. However, recent investigations have revealed the potential role of the microbiome in diseases outside the gastrointestinal tract, such as neurologic, respiratory, and autoimmune diseases. Considering the role of the microbiome in clinical disease and decreased performance associated with respiratory infections, this area of research becomes even more relevant to food animal production. The objective of this paper is to review associations between the gut microbiome and outcome during infectious respiratory disease in animals.

Prevalence of Chlamydia abortus Antibodies in Horses From the Northern State of Mexico and Its Relationship With Domestic Animals

Chlamydia abortus is obligate intracellular bacteria that cause a wide range of reproductive and respiratory diseases in animals and humans. Serologic and molecular evidences of C. abortus in Mexico have been reported in sheep and goats. The presence of C. abortus antibodies in horses (n = 301) was detected by a commercial indirect enzyme-linked immunosorbent assay test. Additionally, C. abortus antibodies in bovines (n = 25), goats (n = 8), and sheep (n = 94) reared with horses were detected to identify probable animal species that could infect horses. The prevalence obtained was 1.32% for horses, 48% for bovines, 12.5% for goats, and 29.7% for sheep. The 75% of horses seropositive to C. abortus were obtained from farms with the presence of sheep seropositive to C. abortus. These results suggest that the presence of C. abortus in horses from Mexico exist and can be related with the presence of sheep positive to C. abortus.

Studying human respiratory disease in animals--role of induced and naturally occurring models.

Respiratory disorders like asthma, emphysema, and pulmonary fibrosis affect millions of Americans and many more worldwide. Despite advancements in medical research that have led to improved understanding of the pathophysiology of these conditions and sometimes to new therapeutic interventions, these disorders are for the most part chronic and progressive; current interventions are not curative and do not halt disease progression. A major obstacle to further advancements relates to the absence of animal models that exactly resemble the human condition, which delays the elucidation of relevant mechanisms of action, the unveiling of biomarkers of disease progression, and identification of new targets for intervention in patients. There are currently many induced animal models of human respiratory disease available for study, and even though they mimic features of human disease, discoveries in these models have not always translated into safe and effective treatments in humans. A major obstacle relates to the genetic, anatomical, and functional variations amongst species, which represents the major challenge to overcome when searching for appropriate models of respiratory disease. Nevertheless, rodents, in particular mice, have become the most common species used for experimentation, due to their relatively low cost, size, and adequate understanding of murine genetics, among other advantages. Less well known is the fact that domestic animals also suffer from respiratory illnesses similar to those found in humans. Asthma, bronchitis, pneumonia, and pulmonary fibrosis are among the many disorders occurring naturally in dogs, cats, and horses, among other species. These models might better resemble the human condition and are emphasized here, but further investigations are needed to determine their relevance.

Bordetella biofilms: a lifestyle leading to persistent infections.

Bordetella bronchiseptica and B. pertussis are Gram-negative bacteria that cause respiratory diseases in animals and humans. The current incidence of whooping cough or pertussis caused by B. pertussis has reached levels not observed since the 1950s. Although pertussis is traditionally known as an acute childhood disease, it has recently resurged in vaccinated adolescents and adults. These individuals often become silent carriers, facilitating bacterial circulation and transmission. Similarly, vaccinated and non-vaccinated animals continue to be carriers of B. bronchiseptica and shed bacteria resulting in disease outbreaks. The persistence mechanisms of these bacteria remain poorly characterized. It has been proposed that adoption of a biofilm lifestyle allows persistent colonization of the mammalian respiratory tract. The history of Bordetella biofilm research is only a decade long and there is no single review article that has exclusively focused on this area. We systematically discuss the role of Bordetella factors in biofilm development in vitro and in the mouse respiratory tract. We further outline the implications of biofilms to bacterial persistence and transmission in humans and for the design of new acellular pertussis vaccines.

The Protein BpsB Is a Poly-β-1,6-N-acetyl-d-glucosamine Deacetylase Required for Biofilm Formation in Bordetella bronchiseptica

Bordetella pertussis and Bordetella bronchiseptica are the causative agents of whooping cough in humans and a variety of respiratory diseases in animals, respectively. Bordetella species produce an exopolysaccharide, known as the Bordetella polysaccharide (Bps), which is encoded by the bpsABCD operon. Bps is required for Bordetella biofilm formation, colonization of the respiratory tract, and confers protection from complement-mediated killing. In this report, we have investigated the role of BpsB in the biosynthesis of Bps and biofilm formation by B. bronchiseptica. BpsB is a two-domain protein that localizes to the periplasm and outer membrane. BpsB displays metal- and length-dependent deacetylation on poly-β-1,6-N-acetyl-d-glucosamine (PNAG) oligomers, supporting previous immunogenic data that suggests Bps is a PNAG polymer. BpsB can use a variety of divalent metal cations for deacetylase activity and showed highest activity in the presence of Ni(2+) and Co(2+). The structure of the BpsB deacetylase domain is similar to the PNAG deacetylases PgaB and IcaB and contains the same circularly permuted family four carbohydrate esterase motifs. Unlike PgaB from Escherichia coli, BpsB is not required for polymer export and has unique structural differences that allow the N-terminal deacetylase domain to be active when purified in isolation from the C-terminal domain. Our enzymatic characterizations highlight the importance of conserved active site residues in PNAG deacetylation and demonstrate that the C-terminal domain is required for maximal deacetylation of longer PNAG oligomers. Furthermore, we show that BpsB is critical for the formation and complex architecture of B. bronchiseptica biofilms.

Farm animal models of organic dust exposure and toxicity: insights and implications for respiratory health.

Modern food animal production is a major contributor to the global economy, owing to advanced intensive indoor production facilities aimed at increasing market readiness and profit. Consequences of these advances are accumulation of dusts, gases, and microbial products that diminish air quality within production facilities. Chronic inhalation exposure contributes to onset and exacerbation of respiratory symptoms and diseases in animals and workers. This article reviews literature regarding constituents of farm animal production facility dusts, animal responses to production building and organic dust exposure, and the effect of chronic inhalation exposure on pulmonary oxidative stress and inflammation. Porcine models of production facility and organic dust exposures reveal striking similarities to observations of human cells, tissues, and clinical data. Oxidative stress plays a key role in mediating respiratory diseases in animals and humans, and enhancement of antioxidant levels through nutritional supplements can improve respiratory health. Pigs are well adapted to the exposures common to swine production buildings and thus serve as excellent models for facility workers. Insight for understanding mechanisms governing organic dust associated respiratory diseases may come from parallel comparisons between farmers and the animals they raise.

Dendritic cells are the major antigen presenting cells in inflammatory lesions of murine mycoplasma respiratory disease and contribute to disease severity (P3306)

Abstract Mycoplasmas cause chronic respiratory diseases in animals and humans, and vaccine development has been problematic. T cell responses were shown to confer protection as well as promote immunopathology in murine mycoplasma pneumonia. Because T cells play a critical role, the role of antigen presenting cells (APC) was examined as they likely influence either an increase in disease severity or promote protective immunity. The roles of APC, such as dendritic cells (DC) and macrophages, in mycoplasma disease are currently unknown. In this study, we examined the ability pulmonary APC populations and their contribution to T cell responses during disease pathogenesis. Both macrophages and DC increased in the lungs of mice after infection. These cell populations showed different patterns of cytokine mRNA expression, supporting the idea that these cells have different impacts on immunity in response to infection. In fact, DC from the lungs of infected mice were most capable of stimulating mycoplasma-specific T helper (Th) cell responses in vitro. In vivo, DC cells were co-localized with Th cells in inflammatory lesions in the lungs of mycoplasma-infected mice. Intratracheal inoculation of mycoplasma antigen-pulsed DC resulted in increased disease severity after subsequent infection. Thus, DC appear to be the major APC population responsible for pulmonary T cell stimulation in mycoplasma-infected mice, and these DC likely contribute to responses impacting disease pathogenesis.