T lymphocyte responses are critical determinants in the pathogenesis and resistance to mycoplasma respiratory disease

Jones, Harlan P.; Simecka, Jerry W.

doi:10.2741/1098

Cited by 22 publications

(13 citation statements)

References 156 publications

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“…Using murine infection with M. pulmonis, the importance of lymphocytes in contributing to the pathology of mycoplasma inflammatory lung disease was demonstrated (21). For example, SCID or nude mice (lacking either T and B cells or T cells alone) infected with M. pulmonis display reduced inflammatory damage (22,23). The depletion of CD4 ϩ , but not CD8 ϩ , T cells reduces disease severity in susceptible (i.e., BALB/c) mice and confirms that T cells dictate the outcome of infection (24).…”

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confidence: 86%

Interleukin-17A Exacerbates Disease Severity in BALB/c Mice Susceptible to Lung Infection with Mycoplasma pulmonis

2018

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Mycoplasmas are atypical bacteria that disrupt the immune response to promote respiratory tract infections and secondary complications. However, not every immunologic response that protects or damages the host during mycoplasma infection is known. Interleukin-17A (IL-17A) is elevated in individuals infected with mycoplasmas, but how IL-17A and its cellular sources dictate disease outcome remains unclear. Here, IL-17A is hypothesized to worsen disease in individuals susceptible to mycoplasma infection. Thus, monoclonal anti-IL-17A antibodies were given to disease-susceptible BALB/c mice and disease-resistant C57BL/6 mice infected with Neutralizing the function of IL-17A using anti-IL-17A antibodies reduced disease severity during infection in BALB/c, but not C57BL/6, mice. Neutralizing IL-17A also reduced the incidence of neutrophilic lung lesions during infection in BALB/c mice. Reduced pathology occurred without impacting the bacterial burden, demonstrating that IL-17A is not required for mycoplasma clearance. The main source of IL-17A throughout infection in BALB/c mice was CD4 T cells, and neutralizing IL-17A after infiltration of the lungs by T cells reduced disease severity, identifying the Th17 response as a herald of late mycoplasma pathology in susceptible mice. Neutralizing IL-17A did not further reduce disease during infection in BALB/c mice depleted of neutrophils, suggesting that IL-17A requires the presence of pulmonary neutrophils to worsen respiratory pathology. IL-17A is a pathological element of murine respiratory mycoplasma infection. Using monoclonal antibodies to neutralize IL-17A could reduce disease severity during mycoplasma infection in humans and domesticated animals.

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confidence: 86%

Interleukin-17A Exacerbates Disease Severity in BALB/c Mice Susceptible to Lung Infection with Mycoplasma pulmonis

2018

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“…As with other mycoplasma diseases, M. pulmonis disease has an immunopathologic element to disease progression. In fact, elements of both the innate [9], [10], [11] and adaptive [12], [13], [14] arms of the immune system play a role in the progression and intrapulmonary clearance of the disease. Thus, it is clear that the mechanisms governing the recruitment of inflammatory cells and control of mycoplasma infection will ultimately determine the severity of mycoplasma respiratory disease.…”

Section: Introductionmentioning

confidence: 99%

Toll-Like Receptor 2 (TLR2) Plays a Major Role in Innate Resistance in the Lung against Murine Mycoplasma

et al. 2010

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Mycoplasma lipoproteins are recognized by Toll-like receptors (TLR), but TLRs' role in responses to infection are unknown. Mycoplasma pulmonis is a naturally occurring respiratory pathogen in mice. In the current study, we used TLR-transfected HEK cells and TLR2−/− bone marrow-derived dendritic cells to demonstrate TLR2-mediated events are important in the initial host-mycoplasma interactions promoting cytokine responses. As we found alveolar macrophages expressed TLR1, TLR2 and TLR6 mRNAs, a role for TLR2 in innate immune clearance in lungs was examined. Three days post-infection, TLR2−/− mice had higher M. pulmonis numbers in lungs, but not in nasal passages. However, TLR2−/− mice had higher lung cytokine levels, indicating TLR2-independent mechanisms are also involved in host responses. Thus, TLR2 plays a critical role in the ability of innate immunity to determine M. pulmonis numbers in the lung, and it is likely that early after respiratory infection that TLR2 recognition of M. pulmonis triggers initial cytokine responses of host cells.

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“…It is clear that elements of the adaptive immune response contribute to the pathology (58, 59), while some responses are protective against M. pulmonis infections (1, 20). Importantly, these responses are determined by the activation of different T cell populations, and the mechanisms that initiate these responses are critical in the pathogenesis of mycoplasma respiratory disease of the lower respiratory tract (19, 60). In a previous study (34), we found that dendritic cells are the major APC population responsible for pulmonary T cell stimulation in mycoplasma-infected mice and likely contribute to responses impacting disease pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Antigen-Pulsed Bone Marrow–Derived and Pulmonary Dendritic Cells Promote Th2 Cell Responses and Immunopathology in Lungs during the Pathogenesis of Murine Mycoplasma Pneumonia

Dobbs

Pulse

Hodge

et al. 2014

The Journal of Immunology

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Mycoplasmas are a common cause of pneumonia in humans and animals, and attempts to create vaccines have not only failed to generate protective host responses, but exacerbated the disease. Mycoplasma pulmonis causes a chronic inflammatory lung disease resulting from a persistent infection, similar to other mycoplasma respiratory diseases. Using this model, Th1 subsets promote resistance to mycoplasma disease and infection, while Th2 responses contribute to immunopathology. The purpose of these studies was to evaluate the capacity of cytokine differentiated dendritic cells (DC) populations to influence the generation of protective and/or pathologic immune responses during M. pulmonis respiratory disease in BALB/c mice. We hypothesized that intratracheal inoculation of mycoplasma antigen-pulsed bone marrow derived dendritic cells (BMDC) could result in the generation of protective T cell responses during mycoplasma infection. However, intratracheal inoculation (priming) of mice with antigen-pulsed DCs resulted enhanced pathology in the recipient mice when challenged with mycoplasma. Inoculation of immunodeficient SCID mice with antigen-pulsed DCs demonstrated that this effect was dependent on lymphocyte responses. Similar results were observed when mice were primed with antigen-pulsed pulmonary, but not splenic, DCs. Lymphocytes generated in uninfected mice after the transfer of either antigen-pulsed BMDCs or pulmonary DCs were shown to be IL13+ Th2 cells, known to be associated with immunopathology. Thus, resident pulmonary DC most likely promote the development of immunopathology in mycoplasma disease through the generation of mycoplasma-specific Th2 responses. Vaccination strategies that disrupt or bypass this process could potentially result in a more effective vaccination.

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T lymphocyte responses are critical determinants in the pathogenesis and resistance to mycoplasma respiratory disease

Cited by 22 publications

References 156 publications

Interleukin-17A Exacerbates Disease Severity in BALB/c Mice Susceptible to Lung Infection with Mycoplasma pulmonis

Interleukin-17A Exacerbates Disease Severity in BALB/c Mice Susceptible to Lung Infection with Mycoplasma pulmonis

Toll-Like Receptor 2 (TLR2) Plays a Major Role in Innate Resistance in the Lung against Murine Mycoplasma

Antigen-Pulsed Bone Marrow–Derived and Pulmonary Dendritic Cells Promote Th2 Cell Responses and Immunopathology in Lungs during the Pathogenesis of Murine Mycoplasma Pneumonia

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