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The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection.

Cunningham K, Stansfield SH, Patel P, Menon S, Kienzle V, Allan JA, Huston WM - BMC Immunol. (2013)

Bottom Line: Chlamydia trachomatis infection results in reproductive damage in some women.PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts.We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Q Block, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia. w.huston@qut.edu.au.

ABSTRACT

Background: Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae.

Results: Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml(-1)) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models.

Conclusions: We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.

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Mouse cells produce IL-6 in response to the chlamydial stress response proteases and Chlamydia. A) The figure shows the IL-6 production from mouse laboratory cell culture mono-layers with McCoy and co-culture with RAW264.7 cells in response to the stimulants. B) The graph shows the IL-6 production by primary uterine horn and caudal lymph node mouse cell culture in response to the stimulants. Stimulants are indicated to the right of each graph by the shaded bars (n = 2).
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Figure 5: Mouse cells produce IL-6 in response to the chlamydial stress response proteases and Chlamydia. A) The figure shows the IL-6 production from mouse laboratory cell culture mono-layers with McCoy and co-culture with RAW264.7 cells in response to the stimulants. B) The graph shows the IL-6 production by primary uterine horn and caudal lymph node mouse cell culture in response to the stimulants. Stimulants are indicated to the right of each graph by the shaded bars (n = 2).

Mentions: Mice fibroblasts (McCoy) and mice macrophages (RAW264.7) were then tested to ensure the C. muridarum proteins also induce IL-6 from mice cells. Other than IL-6 we were able to detect IL-10, GM-CSF, TNFα production in response to the proteins and Chlamydia (Additional file 4: Figure S4). None or physiologically irrelevant levels of cytokine was detected for IL-2, IL-4, IL-5, IL-6, IL-12, or IFN-γ under all conditions. The secreted levels of IL-6, IL-10, GM-CSF, and TNFα were all increased in the co-culture models compared to individual cell cultures when the stimulant was CmHtrA or CmTsp (Figure 5, and Additional file 4: Figure S4). However, for live Chlamydia the amount of IL-6 was reduced in co-culture models compared to the mono-cultures alone (Figure 5), consistent with what we already observed with the human cell culture models (Figures 1 and 2).


The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection.

Cunningham K, Stansfield SH, Patel P, Menon S, Kienzle V, Allan JA, Huston WM - BMC Immunol. (2013)

Mouse cells produce IL-6 in response to the chlamydial stress response proteases and Chlamydia. A) The figure shows the IL-6 production from mouse laboratory cell culture mono-layers with McCoy and co-culture with RAW264.7 cells in response to the stimulants. B) The graph shows the IL-6 production by primary uterine horn and caudal lymph node mouse cell culture in response to the stimulants. Stimulants are indicated to the right of each graph by the shaded bars (n = 2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4225670&req=5

Figure 5: Mouse cells produce IL-6 in response to the chlamydial stress response proteases and Chlamydia. A) The figure shows the IL-6 production from mouse laboratory cell culture mono-layers with McCoy and co-culture with RAW264.7 cells in response to the stimulants. B) The graph shows the IL-6 production by primary uterine horn and caudal lymph node mouse cell culture in response to the stimulants. Stimulants are indicated to the right of each graph by the shaded bars (n = 2).
Mentions: Mice fibroblasts (McCoy) and mice macrophages (RAW264.7) were then tested to ensure the C. muridarum proteins also induce IL-6 from mice cells. Other than IL-6 we were able to detect IL-10, GM-CSF, TNFα production in response to the proteins and Chlamydia (Additional file 4: Figure S4). None or physiologically irrelevant levels of cytokine was detected for IL-2, IL-4, IL-5, IL-6, IL-12, or IFN-γ under all conditions. The secreted levels of IL-6, IL-10, GM-CSF, and TNFα were all increased in the co-culture models compared to individual cell cultures when the stimulant was CmHtrA or CmTsp (Figure 5, and Additional file 4: Figure S4). However, for live Chlamydia the amount of IL-6 was reduced in co-culture models compared to the mono-cultures alone (Figure 5), consistent with what we already observed with the human cell culture models (Figures 1 and 2).

Bottom Line: Chlamydia trachomatis infection results in reproductive damage in some women.PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts.We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Q Block, 60 Musk Ave, Kelvin Grove, QLD 4059, Australia. w.huston@qut.edu.au.

ABSTRACT

Background: Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae.

Results: Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml(-1)) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models.

Conclusions: We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism.

Show MeSH
Related in: MedlinePlus