Bronchus-associated Lymphoid Tissue Research Articles

Organized lymphatic tissue (BALT) in lungs of rhesus monkeys after air pollutant exposure.

The presence of bronchus-associated lymphoid tissue (BALT) and its size in humans largely depends upon age. It is detected in 35% of children less than 2 years of age, but absent in the healthy adult lung. Environmental gases or allergens may have an effect on the number of BALT. Lungs of rhesus macaque monkeys were screened by histology for the presence, size, and location of BALT after exposure to filtered air for 2, 6, 12, or 36 months or 12 and 36 months to ozone or 2, 12, or 36 months of house dust mite or a combination of ozone and house dust mite for 12 months. In the lungs of monkeys housed in filtered air for 2 months, no BALT was identified. After 6, 12, or 36 months, the number of BALT showed a significantly increased correlation with age in monkeys housed in filtered air. After 2 months of episodic house dust mite (HDM) exposure, no BALT was found. Monkeys exposed to HDM or HDM + ozone did not show a significant increase in BALT compared to monkeys housed in filtered air. However, monkeys exposed to ozone alone did show significant increases in BALT compared to all other groups. In particular, there were frequent accumulations of lymphocytes in the periarterial space of ozone exposed animals. In conclusion, BALT in rhesus monkeys housed under filtered air conditions is age-dependent. BALT significantly increased in monkeys exposed to ozone in comparison with monkeys exposed to HDM.

Formation of Lung Inducible Bronchus Associated Lymphoid Tissue Is Regulated by Mycobacterium tuberculosis Expressed Determinants.

Mycobacterium tuberculosis (Mtb) is the causative agent of the infectious disease tuberculosis (TB), which is a leading cause of death worldwide. Approximately one fourth of the world's population is infected with Mtb. A major unresolved question is delineating the inducers of protective long-lasting immune response without inducing overt, lung inflammation. Previous studies have shown that the presence of inducible Bronchus-Associated Lymphoid Tissue (iBALT) correlate with protection from Mtb infection. In this study, we hypothesized that specific Mtb factors could influence the formation of iBALT, thus skewing the outcome of TB disease. We infected non-human primates (NHPs) with a transposon mutant library of Mtb, and identified specific Mtb mutants that were over-represented within iBALT-containing granulomas. A major pathway reflected in these mutants was Mtb cell wall lipid transport and metabolism. We mechanistically addressed the function of one such Mtb mutant lacking mycobacteria membrane protein large 7 (MmpL7), which transports phthiocerol dimycocerosate (PDIM) to the mycobacterial outer membrane (MOM). Accordingly, murine aerosol infection with the Mtb mutant Δmmpl7 correlated with increased iBALT-containing granulomas. Our studies showed that the Δmmpl7 mutant lacking PDIMs on the surface overexpressed diacyl trehaloses (DATs) in the cell wall, which altered the cytokine/chemokine production of epithelial and myeloid cells, thus leading to a dampened inflammatory response. Thus, this study describes an Mtb specific factor that participates in the induction of iBALT formation during TB by directly modulating cytokine and chemokine production in host cells.

Development and organization of pulmonary lymphoid aggregates after Klebsiella pneumoniae infection of the murine respiratory tract

Abstract Klebsiella pneumoniae is a worrisome nosocomial pathogen given the widespread emergence of antibiotic resistant strains. Little is known about the host immune response to K. pneumoniae; however, it has recently been shown that aggregates of lymphoid cells can be found in murine lungs 4 weeks after surviving K. pneumoniae pulmonary infection. Others have characterized pulmonary collections of lymphoid cells in response to other pathogens and coined them induced bronchus-associated lymphoid tissue (iBALT). iBALT is believed to assist in protection against re-infection. In our nonlethal model of K. pneumoniae, mice that survive the primary infection and exhibit these structures are indeed protected from K. pneumoniae challenge. To further characterize the development and organization of these structures, pulmonary immune cell populations were analyzed post-infection by flow cytometry, histology, and immunofluorescence. As expected, pulmonary neutrophil populations increase over the first 10 days post-infection. T cells appear to rapidly expand between 7 and 10 days post-infection and both CD4+ and γδ T cell subsets make up the majority of this population. Immunofluorescent imaging of lymphoid aggregates demonstrate that CD4+ and γδ T cells are found within these structures at early time-points. Experiments using TCRβδ−/− mice lacking T cells reveals the absence of lymphoid aggregates 28 days post-infection, suggesting that T cells are essential in the initial formation and development of these structures.

Transient immunosuppression blocks iBALT formation in the lung induced by helper-dependent adenoviral vector during gene delivery

Abstract Lung is an immune sensitive organ with presence of all immune cells at the frontline of immunity. Under chronic infection conditions, inducible Bronchus-associated lymphoid tissue (iBALT) can be formed to defend foreign infectious organisms. We wonder whether viral vectors for gene therapy could induce iBALT formation and whether this process can be controlled through immune modulation. To test these ideas, we repeatedly administered a helper-dependent adenoviral (HD-Ad) vector to mouse lungs and examined iBALT formation. HD-Ad vectors are based on adenovirus but with all viral coding sequences deleted and is one option for large gene delivery. In our previous studies, HD-Ad vectors have exhibited high in vivo efficiency in transduction of mouse, rabbit and pig airway epithelial cells, including stem/progenitor cells such as basal cells. HD-Ad vectors expressing therapeutic gene encoding cystic fibrosis transmenbrane conductance regulator (CFTR) rescue CFTR function in CF patient primary cells. In our mouse studies, we found that HD-Ad vectors induced iBALT formation and antibody production. We used cyclophosphamide or HD-Ad expressing IL-10 to modulate the host immune responses and to examine the effects on iBALT formation. Comparing with control group (HD-Ad vectors only), the mice treated with cyclophosphamide or IL-10 expressing HD-Ad vector showed a significant reduction of iBALT formation and infiltration of inflammatory cells, including CD4+ and B220+ as well as production of anti-Ad antibodies and neutralizing antibodies. Our results indicate that transient modulation significantly mitigated immunopathology and extended transgene expression in mouse airways following readministration of HD-Ad vectors.

COVID-19 in children: the link in the transmission chain

COVID-19 in children: the link in the transmission chain

Immunohistochemical and Ultrastructural Studies of Mycoplasma hyopneumoniae Strain in Naturally Infected Pigs in Nigeria

Abstract Enzootic pneumonia caused by hyopneumoniae (MHYO) remains a serious concern to the swine industry in many countries including Nigeria. MHYO strains isolated from pigs from different countries and geographical locations are known to vary in pathogenicity. There is a paucity of information on the pathogenicity of the MHYO strain affecting pigs in Nigeria. This study investigated the pathogenicity of the MHYO strain in naturally infected pigs using immunohisto-chemistry and electron microscopy. Two hundred and sixty four lungs of slaughtered pigs were randomly collected from abattoirs at Abeokuta, Ibadan and Lagos, in Southwest Nigeria. A sub-sample of 104 pneumonic and 20 apparently normal lungs was selected, processed for routine histopathological examination and immunohistochemistry, while 3 lung tissues samples were selected for ultrastructural studies. The most significant microscopic changes observed were suppurative broncho-interstitial pneumonia associated with varying degrees of lymphoid hyperplasia of the bronchus-associated lymphoid tissue (BALT) and thickened alveolar septa due to cellular infiltration consisting predominantly of neutrophils and a few mononuclear cells. Immunohistochemically, MHYO antigen was detected in 86/104 (82.69 %) of MHYO-infected lung tissues and typically exhibited a granular brown reaction on the bronchial and bronchiolar epithelial lining, mononuclear cells in the BALT and luminal cellular exudates within the airways. Transmission electron microscopy revealed numerous Mycoplasma organisms in the lumina of the airways, in between degenerated cilia, while a few Mycoplasmas were located within the alveoli. It was concluded that the MHYO strain detected in this study was pathogenic to pigs and capable of inducing pneumonia, and therefore implicated in the pathogenesis.

Type II Epithelial RhoA Protects against Allergic Airway inflammation and the Formation of Inducible Bronchus-Associated Lymphoid Tissue (iBALT)

Type II Epithelial RhoA Protects against Allergic Airway inflammation and the Formation of Inducible Bronchus-Associated Lymphoid Tissue (iBALT)

ACKR2 contributes to pulmonary dysfunction by shaping CCL5:CCR5-dependent recruitment of lymphocytes during influenza A infection in mice

Inflammation triggered by influenza A virus (IAV) infection is important for viral clearance, induction of adaptive responses, and return to lung homeostasis. However, an exaggerated immune response, characterized by the overproduction of chemokines, can lead to intense lung injury, contributing to mortality. Chemokine scavenger receptors, such as ACKR2, control the levels of CC chemokines influencing the immune responses. Among the chemokine targets of ACKR2, CCL5 is important to recruit and activate lymphocytes. We investigated the role of ACKR2 during IAV infection in mice. Pulmonary ACKR2 expression was increased acutely after IAV infection preceding the virus-induced lung dysfunction. ACKR2-knockout (ACKR2-/-) mice were protected from IAV, presenting decreased viral burden and lung dysfunction. Mechanistically, the absence of ACKR2 resulted in augmented airway CCL5 levels, secreted by mononuclear and plasma cells in the lung parenchyma. The higher chemokine gradient led to an augmented recruitment of T and B lymphocytes, formation of inducible bronchus-associated lymphoid tissue and production of IgA in the airways of ACKR2-/- mice post-IAV. CCL5 neutralization in ACKR2-/- mice prevented lymphocyte recruitment and increased bronchoalveolar lavage fluid protein levels and pulmonary dysfunction. Finally, CCR5-/- mice presented increased disease severity during IAV infection, displaying increased neutrophils, pulmonary injury and dysfunction, and accentuated lethality. Collectively, our data showed that ACKR2 dampens CCL5 levels and the consequent recruitment of CCR5+ T helper 1 (Th1), T regulatory cells (Tregs), and B lymphocytes during IAV infection, decreasing pathogen control and promoting lung dysfunction in wild type mice. Therefore, ACKR2 is detrimental and CCR5 is protective during IAV infection coordinating innate and adaptive immune responses in mice.

Follicular Bronchiolitis: Two Cases with Varying Clinical and Radiological Presentation

Follicular bronchiolitis (FB) is a rare bronchiolar disorder associated with hyperplasia of the bronchial-associated lymphoid tissue (BALT). It is characterized by the development of lymphoid follicles with germinal centers in the walls of small airways. It falls under the category of lymphoproliferative pulmonary diseases (LPDs) and commonly occurs in relation to connective tissue disease, immunodeficiency, infections, interstitial lung disease (ILD), and inflammatory airway diseases. Computerized tomography (CT) findings include centrilobular nodules with patchy ground glass infiltrate, tree-in-bud findings, and air trapping. It can very rarely present as diffuse cystic lung disease. We present two cases of FB. The first case is associated with Human Immunodeficiency Virus (HIV) infection and asthma with diffuse cystic changes on the CT. The second case is associated with reactive airway disease and gastroesophageal reflux disease (GERD) with the classic centrilobular nodules and ground glass opacities on the CT.

Bronchus-associated lymphoid tissue（BALT）リンパ腫と再評価された下部気管の隆起性病変の1例

Bronchus-associated lymphoid tissue（BALT）リンパ腫と再評価された下部気管の隆起性病変の1例

IL-22 is required for the induction of bronchus-associated lymphoid tissue in tolerant lung allografts.

Long-term survival after lung transplantation remains profoundly limited by graft rejection. Recent work has shown that bronchus-associated lymphoid tissue (BALT), characterized by the development of peripheral nodal addressin (PNAd)-expressing high endothelial venules and enriched in B and Foxp3+ T cells, is important for the maintenance of allograft tolerance. Mechanisms underlying BALT induction in tolerant pulmonary allografts, however, remain poorly understood. Here, we show that the development of PNAd-expressing high endothelial venules within intragraft lymphoid follicles and the recruitment of B cells, but not Foxp3+ cells depends on IL-22. We identify graft-infiltrating gamma-delta (γδ) T cells and Type 3 innate lymphoid cells (ILC3s) as important producers of IL-22. Reconstitution of IL-22 at late time points through retransplantation into wildtype hosts mediates B cell recruitment into lymphoid follicles within the allograft, resulting in a significant increase in their size, but does not induce PNAd expression. Our work has identified cellular and molecular requirements for the induction of BALT in pulmonary allografts during tolerance induction and may provide a platform for the development of new therapies for lung transplant patients.

Enhancement of immune response against Bordetella spp. by disrupting immunomodulation

Well-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the respiratory tract of mice, its natural host, but did increase activation of the inflammasome pathway, and recruitment of inflammatory cells. The mutant lacking btrS recruited many more B and T cells into the lungs, where they rapidly formed highly organized and distinctive Bronchial Associated Lymphoid Tissue (BALT) not induced by any wild type Bordetella species, and a much more rapid and strong antibody response than observed with any of these species. Immunity induced by the mutant was measurably more robust in all respiratory organs, providing completely sterilizing immunity that protected against challenge infections for many months. Moreover, the mutant induced sterilizing immunity against infection with other classical bordetellae, including B. pertussis and B. parapertussis, something the current vaccines do not provide. These findings reveal profound immunomodulation by bordetellae and demonstrate that by disrupting it much more robust protective immunity can be generated, providing a pathway to greatly improve vaccines and preventive treatments against these important pathogens.

Expectant Management of Extranodal Marginal Zone Lymphoma of Bronchial-Associated Lymphoid Tissue (BALT)

Expectant Management of Extranodal Marginal Zone Lymphoma of Bronchial-Associated Lymphoid Tissue (BALT)

Cross-sectional study of seropositivity, lung lesions and associated risk factors of the main pathogens of Porcine Respiratory Diseases Complex (PRDC) in Goi\xe1s, Brazil

BackgroundThe objective of the study was to evaluate the occurrence and severity of Porcine Respiratory Diseases Complex (PRDC) pathogens in the Goiás State, Brazil. Were assessed the serological antibodies occurrency of Mycoplasma hyopneumoniae, Actinobacillus pleuropneumoniae and swine influenza virus (SIV), as well as the evaluation of pulmonary Mycoplasma-like lung lesions, pleuritis, histopathological lesions and diseases occurrence associated with risk factors, such as management, housing and productive indexes. We conveniently selected 2536 animals for serology testing, and 900 lungs at slaughtering of animals from 30 multisite herds in Goiás State, Brazil.ResultsFor M. hyopneumoniae, all herds presented seropositive animals at some stage of production. Even though most herds (29/30) vaccinated against this pathogen, 90.0% (27/30) of the herds presented at least 50.0% of seropositive animals in finishing and slaughter. Overall, antibodies against A. pleuropneumoniae were present in lower occurrence, varying from 22.4% of the animals in the nursery phase to 1.3% of the animals at slaughter. Conversely, SIV circulated in most herds, with 29 seropositive herds without vaccination. The occurrence of anti-SIV antibodies was higher at slaughter (74.5% of the animals) than nursery (41.8% of the animals), and at slaughter, 23 herds (76.7%) presented at least 50.0% of seropositive animals. All herds presented animals with pulmonary Mycoplasma-like lung lesions, and of the 900 lungs evaluated in the slaughterhouse, 665 (73.9%) presented an average Mycoplasma-like lung lesions of 7.3%. Evaluations of the pneumonia index (PI) showed that 73.3% of the herds were strongly affected by a pathology that manifested itself in different presentation forms. Microscopically, there was a predominance of bronchopneumonia lesions (74.6% of affected lungs), with a high occurrence of the chronic form (57.1%), and there was a moderate to marked proliferation of bronchial associated lymphoid tissue (BALT) in 64.1% of the affected lungs. Pleuritis were observed in 13.5% of the animals.ConclusionSerological tests evidenced that antibodies against App and SIV were present in the Goiás State herds, and high occurrence of M. hyopneumoniae antibodies in finishing phases and slaughter may be influenced by pathogen circulation in vaccinated herds, leading to respiratory lesions at slaughter. Additionally, swine influenza virus was broadly disseminated in technified herds in Goiás State.

Intranasal inoculation of recombinant DNA vaccine ABA392 against haemorrhagic septicaemia disease.

We evaluate the efficacy of recombinant DNA vaccine ABA392 against haemorrhagic septicaemia infection through intranasal administration route by targeting the mucosal immunity. The DNA vaccine was constructed and subjected to animal study using the Sprague Dawley (SD) rat. The study was divided into two major parts: (i) active and (ii) passive immunization studies, involving 30 animals for each part. Each group was then divided into five test groups: two test samples G1 and G2 with 50 and 100µgml-1 purified DNA vaccine; one positive control G5 with 106 CFU per ml formalin-killed PMB2; and two negative controls, G3 and G4 with normal saline and pVAX1 vector. Both studies were conducted for the determination of immunogenicity by total white blood cell count (TWBC), indirect ELISA and histopathological changes for the presence of the bronchus-associated lymphoid tissue (BALT). Our findings demonstrate that TWBC, IgA and IgG increased after each of the three vaccination regimes: groups G1, G2 and G5. Test samples G1 and G2 showed significant differences (P<0·05) compared to the negative controls, G3 and G4, but no significant differences from the positive control G5. Groups G1, G2 and G5 showed more formation of BALT compared to the negative controls, G3 and G4. Our results show that intranasal inoculation of recombinant DNA vaccine ABA392 can provoke mucosal immunity which makes it a potential prophylactic against HS. SIGNIFICANCE AND IMPACT OF THE STUDY: New approach of combating haemorrhagic septicaemia disease among bovines by recombinant DNA vaccine is crucial to overcome the loss of edible products from the infected bovines. DNA vaccine can potentially serve as a better immunogen which would elicit both cellular and humoral immunity, and it is also stable for its molecular reproduction. This research report demonstrates an effective yet simple way of administering the DNA vaccine via the intranasal route in rats, to provoke the mucosal immunity through the development of immunoglobulins IgA, IgG and bronchus-associated lymphoid tissue which guard as the first-line defence at the host's mucosal lining.

Primary pulmonary lymphoma from bronchus-associated lymphoid tissue (clinical observation)

Purpose. To describe the clinical case of rare indolent extranodal non-Hodgkin’s lymphoma, which originates from bronchus-associated lymphoid tissue, and to analyze the main current trends in the diagnosis and treatment of this pathology.Using bibliosemantic and analytical methods of research in modern scientific literature, we analyzed the main historical data and clinical-radiological and immunomorphological criteria for the diagnosis of casuistically rare neoplasm – the primary pulmonary non-Hodgkin's lymphoma – the indolent extranodal B-cell lymphoma of the marginal zone, arising from the bronchus-associated lymphoid tissue (BALT). The prevalence of BALT-lymphoma is less than 0.5 % of all pulmonary malignant tumors and less than 1 % of all non-Hodgkin’s lymphomas. Nowadays, diagnostic approaches and standard systemic treatment of this disease are still widely discussed. The recommendations of the retrospective international study of primary extranodal lymphoma of lungs from the marginal zone conducted by the international extranodal lymphoma study group (IELSG) are presented and the main recommendations of the NCCN for the diagnosis and treatment of mucosa-associated lymphoma (2019) are analyzed. Treatment options for BALT-lymphomas vary in the range from antibiotic therapy and clinical observation to surgical resection or combination with chemotherapy and radiotherapy, but optimal therapy for the disease needs further study. It is noted that precise morphological definition and immunohistochemical phenotyping allow choosing an adequate protocol for chemo-therapeutic treatment (immunochemotherapy). The main options for radical surgical, chemo-therapeutic and radiological stages of BALT-lymphoma treatment and indications for their combined use within the framework of the multidisciplinary approach to treatment with lymphomas are discussed and their effectiveness is determined. The actual 4-year clinical observation of 48 year old patient with BALT-lymphoma is presented and the main radiological diagnostic criteria and difficulties of morphological diagnostics and immunohistochemical phenotyping are discussed. The above clinical observation is aimed at information of a wide range of practicing doctors – therapists, pulmonologists, phthisiologists, thoracic surgeons, oncologists, radiologists.Conclusions. BALT-lymphoma is a rare form of extranodal non-Hodgkin’s lymphoma, that does not have clear clinical guidelines and specific radiological signs and requires well-balanced histological diagnostics and immunohistochemical verification, which, in combination with computed tomography (PET-CT) methods, determines the stage of the disease and, respectively, tactics for the management of patients.

Quorum quenching intervened in vivo attenuation and immunological clearance enhancement by Solanum torvum root extract against Pseudomonas aeruginosa instigated pneumonia in Sprague Dawley rats

BackgroundPseudomonas aeruginosa have been delineated for its disreputable charisma in nosocomial infections leading to pulmonary pneumonia. The recent developments in multi-drug resistance accelerate the need of alternative antibacterial strategies. In this study we analysed the efficacy of quorum quenching mediated bacterial silencing in effective immunological clearance upon pulmonary infected rat models.ResultsQuorum sensing inhibitor was extracted from Solanum torvum which is a native plant in Kerala, India. The in vitro pilot studies upon Pseudomonas aeruginosa strain jb07 revealed the ability of Solanum torvum root extract (STRE) to successfully inhibit quorum sensing controlled virulent factors such as chromogenesis and biofilm formation; though the bacterial growth was unaffected. In vivo analysis upon Sprague Dawley rats shown the potential of STRE in aiding successful bacterial clearance where in cent percentage of survival was evident that compared with untreated group. Subjects treated with STRE possessed natural immunological response with inflammation, MNC infiltration and BALT (bronchus associated lymphoid tissue) hyperplasia unlike the Ciprofloxacin treated comparative group.ConclusionsThe observations of this study suggests that STRE is not having any bactericidal activity rather its silencing the infectant in a system which in turn disables the virulence of bacteria and remain attenuated; therefore immune system get adequate time for successful countermeasures.

Silver nanoparticle-adjuvanted vaccine protects against lethal influenza infection through inducing BALT and IgA-mediated mucosal immunity

Most of current influenza virus vaccines fail to develop a strong immunity at lung mucosae (site of viral entry) due to sub-optimal vaccination protocols (e.g. inactivated virus administered by parenteral injections). Mucosal immunity could be improved by using locally-delivered vaccines containing appropriate adjuvants. Here we show, in a mouse model, that inclusion of silver nanoparticles (AgNPs) in virus-inactivated flu vaccine resulted in reduction of viral loads and prevention of excessive lung inflammation following influenza infection. Concomitantly, AgNPs enhanced specific IgA secreting plasma cells and antibodies titers, a hallmark of successful mucosal immunity. Moreover, vaccination in the presence of AgNPs but not with gold nanoparticles, protected mice from lethal flu. Compared with other commercial adjuvants (squalene/oil-based emulsion) or silver salts, AgNPs stimulated stronger antigen specific IgA production with lower toxicity by promoting bronchus-associated lymphoid tissue (BALT) neogenesis, and acted as a bona fide mucosal adjuvant.

Airway M Cells Arise in the Lower Airway Due to RANKL Signaling and Reside in the Bronchiolar Epithelium Associated With iBALT in Murine Models of Respiratory Disease.

Microfold (M) cells residing in the follicle-associated epithelium of mucosa-associated lymphoid tissues are specialized for sampling luminal antigens to initiate mucosal immune responses. In the past decade, glycoprotein 2 (GP2) and Tnfaip2 were identified as reliable markers for M cells in the Peyer's patches of the intestine. Furthermore, RANKL–RANK signaling, as well as the canonical and non-canonical NFκB pathways downstream, is essential for M-cell differentiation from the intestinal stem cells. However, the molecular characterization and differentiation mechanisms of M cells in the lower respiratory tract, where organized lymphoid tissues exist rarely, remain to be fully elucidated. Therefore, this study aimed to explore M cells in the lower respiratory tract in terms of their specific molecular markers, differentiation mechanism, and functions. Immunofluorescence analysis revealed a small number of M cells expressing GP2, Tnfaip2, and RANK is present in the lower respiratory tract of healthy mice. The intraperitoneal administration of RANKL in mice effectively induced M cells, which have a high capacity to take up luminal substrates, in the lower respiratory epithelium. The airway M cells associated with lymphoid follicles were frequently detected in the pathologically induced bronchus-associated lymphoid tissue (iBALT) in the murine models of autoimmune disease as well as pulmonary emphysema. These findings demonstrate that RANKL is a common inducer of M cells in the airway and digestive tracts and that M cells are associated with the respiratory disease. We also established a two-dimensional culture method for airway M cells from the tracheal epithelium in the presence of RANKL successfully. This model may be useful for functional studies of M cells in the sampling of antigens at airway mucosal surfaces.

Inflammation induced by different plasmid types of russian &lt;i&gt;Yersinia pseudotuberculosis&lt;/i&gt; strains

In the 2000s, a scientific interest to the Far Eastern scarlet-like fever (FESLF) mainly recorded In Russia and Japanwas remarkably increased. Such clinical and epidemic manifestation of human pseudotuberculosis is related to a certain bacterial clonal lineage characterized by a specific plasmid profile (pVM82, pYV48), sequence type (2ST) as well as the yadA gene allele (1st allele). In our study we examined features of inflammatory changes characterizing plasmidassociated pathogenicity of the FESLF pathogen. In addition, organ histopathology in experimental animals infected intraperitoneally with Y. pseudotuberculosis strains of the four plasmid types 48+:82+; 48+:82-; 48-:82+; 48-:82-; and 48-:82- was investigated. It was found that the mortality rate in animals infected with Y. pseudotuberculosis H-5015 strain (82+:48+) bearing two plasmids with a molecular weight of 82 and 48 MDa was 40%. A picture of diffuse pneumonia with moderate inflammatory infiltration in pulmonary tissue and changes in lymphoid organs characterizing immunodeficiency we observed as early as 3 days postinfection (p.i.). On the contrary, animals infected with Y. pseudotuberculosis H-5015 strain (82+:48) bearing a single plasmid 82 MDa pVM, mortality rate was 30%. A vascular reaction in the lungs and liver as well as deteriorated vascular destructive changes were revealed starting from day 3 and on day 57 days p.i., respectively, which was paralleled with perivascular infiltration mainly by mononuclear cells and focal pneumonia as well as a reaction of bronchialassociated lymphoid tissue and minimal organ destructive changes. On day 7 p.i., signs of granulomatous inflammation in the liver in a form of small mononuclear cell clusters and perivascular compact infiltrates were found. At all time points, lymphoid organ hyperplasia was noted. In case the infection caused by H-5013 strain (48+), the mortality rate was 80%. Inflammatory changes with dominant mononuclear cells were detected as early as 1 day p.i. associated with a picture of large focal bronchopneumonia, more pronounced in the non-survivor animals, also demonstrating signs of severe immunosuppression in the lymphoid organs. Starting from day 3 p.i., lymphoid hypoplasia in the spleen and lymph nodes was detected in all infected animals paralleled with pathogen-associated tissue damage in various organs. Animals infected with the plasmid-free H-5013 strain 48-) resulted in 25% mortality rate. Moreover, starting from day 3 p.i., a slight mononuclear inflammatory infiltration in the lungs and liver, a moderate giant cell reaction in the splenic pulp, and loose perinodal inflammatory infiltration in the lymph nodes were observed. Thus, while modeling infection caused by different plasmid types of Y. pseudotuberculosis, the data on differences in histopathology of changes in diverse organs regarding dynamics and generalization of the inflammatory response, as well as the severity of pathogen-associated damage in the lymphoid tissue were obtained. In case Y. pseudotuberculosis strains contained pVM82 plasmid with or without virulence plasmid pYV vs. single pYV-positive strains, an area of the inflammatory response as well as severity of immunosuppression manifested by splenic and lymph node delymphatization were decreased. It allowed to suggest that pVM82 plasmid found In Russia-originating Y. pseudotuberculosis strains might be implicated in limiting intensity of inflammatory response, bacterial dissemination and severity of lymphoid organ damage.