A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci.
The complement system modulates the intensity of innate and specific immunity. While it protects against infections by extracellular bacteria its role in infection with obligate intracellular bacteria, such as the avian and human pathogen Chlamydia (C.) psittaci, is still unknown. In the present stu...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3506576?pdf=render |
| _version_ | 1818516684523175936 |
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| author | Jenny Bode Pavel Dutow Kirsten Sommer Katrin Janik Silke Glage Burkhard Tümmler Antje Munder Robert Laudeley Konrad W Sachse Andreas Klos |
| author_facet | Jenny Bode Pavel Dutow Kirsten Sommer Katrin Janik Silke Glage Burkhard Tümmler Antje Munder Robert Laudeley Konrad W Sachse Andreas Klos |
| author_sort | Jenny Bode |
| collection | DOAJ |
| description | The complement system modulates the intensity of innate and specific immunity. While it protects against infections by extracellular bacteria its role in infection with obligate intracellular bacteria, such as the avian and human pathogen Chlamydia (C.) psittaci, is still unknown. In the present study, knockout mice lacking C3 and thus all main complement effector functions were intranasally infected with C. psittaci strain DC15. Clinical parameters, lung histology, and cytokine levels were determined. A subset of infections was additionally performed with mice lacking C5 or C5a receptors. Complement activation occurred before symptoms of pneumonia appeared. Mice lacking C3 were ∼100 times more susceptible to the intracellular bacteria compared to wild-type mice, with all C3(-/-) mice succumbing to infection after day 9. At a low infective dose, C3(-/-) mice became severely ill after an even longer delay, the kinetics suggesting a so far unknown link of complement to the adaptive, protective immune response against chlamydiae. The lethal phenotype of C3(-/-) mice is not based on differences in the anti-chlamydial IgG response (which is slightly delayed) as demonstrated by serum transfer experiments. In addition, during the first week of infection, the absence of C3 was associated with partial protection characterized by reduced weight loss, better clinical score and lower bacterial burden, which might be explained by a different mechanism. Lack of complement functions downstream of C5 had little effect. This study demonstrates for the first time a strong and complex influence of complement effector functions, downstream of C3 and upstream of C5, on the outcome of an infection with intracellular bacteria, such as C. psittaci. |
| first_indexed | 2024-12-11T00:45:30Z |
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| id | doaj.art-23899fc03adc4c63a88a4853eb0f1e5d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T00:45:30Z |
| publishDate | 2012-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-23899fc03adc4c63a88a4853eb0f1e5d2022-12-22T01:26:47ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e5032710.1371/journal.pone.0050327A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci.Jenny BodePavel DutowKirsten SommerKatrin JanikSilke GlageBurkhard TümmlerAntje MunderRobert LaudeleyKonrad W SachseAndreas KlosThe complement system modulates the intensity of innate and specific immunity. While it protects against infections by extracellular bacteria its role in infection with obligate intracellular bacteria, such as the avian and human pathogen Chlamydia (C.) psittaci, is still unknown. In the present study, knockout mice lacking C3 and thus all main complement effector functions were intranasally infected with C. psittaci strain DC15. Clinical parameters, lung histology, and cytokine levels were determined. A subset of infections was additionally performed with mice lacking C5 or C5a receptors. Complement activation occurred before symptoms of pneumonia appeared. Mice lacking C3 were ∼100 times more susceptible to the intracellular bacteria compared to wild-type mice, with all C3(-/-) mice succumbing to infection after day 9. At a low infective dose, C3(-/-) mice became severely ill after an even longer delay, the kinetics suggesting a so far unknown link of complement to the adaptive, protective immune response against chlamydiae. The lethal phenotype of C3(-/-) mice is not based on differences in the anti-chlamydial IgG response (which is slightly delayed) as demonstrated by serum transfer experiments. In addition, during the first week of infection, the absence of C3 was associated with partial protection characterized by reduced weight loss, better clinical score and lower bacterial burden, which might be explained by a different mechanism. Lack of complement functions downstream of C5 had little effect. This study demonstrates for the first time a strong and complex influence of complement effector functions, downstream of C3 and upstream of C5, on the outcome of an infection with intracellular bacteria, such as C. psittaci.http://europepmc.org/articles/PMC3506576?pdf=render |
| spellingShingle | Jenny Bode Pavel Dutow Kirsten Sommer Katrin Janik Silke Glage Burkhard Tümmler Antje Munder Robert Laudeley Konrad W Sachse Andreas Klos A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci. PLoS ONE |
| title | A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci. |
| title_full | A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci. |
| title_fullStr | A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci. |
| title_full_unstemmed | A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci. |
| title_short | A new role of the complement system: C3 provides protection in a mouse model of lung infection with intracellular Chlamydia psittaci. |
| title_sort | new role of the complement system c3 provides protection in a mouse model of lung infection with intracellular chlamydia psittaci |
| url | http://europepmc.org/articles/PMC3506576?pdf=render |
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