Immunobiology of monocytes and macrophages during Chlamydia trachomatis infection

Lausen, Mads; Christiansen, Gunna; Poulsen, Thomas B.; Birkelund, Svend

doi:10.1016/j.micinf.2018.10.007

Cited by 22 publications

(19 citation statements)

References 107 publications

(102 reference statements)

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“…The ability of bacterial pathogens to establish a chronic infection and stably colonize the host requires evasion of the host immune response. During chlamydial infection of the genitourinary tract, macrophages and monocytes are recruited to the site of infection by following the chemoattractant gradient of cytokines and chemokines produced by infected epithelial cells (Darville and Hiltke, 2010;Lausen et al, 2018). Efficient phagocytosis and killing of bacteria by macrophages and other phagocytes are necessary to prevent the spread and dissemination of chlamydiae.…”

Section: Discussionmentioning

confidence: 99%

“…Efficient phagocytosis and killing of bacteria by macrophages and other phagocytes are necessary to prevent the spread and dissemination of chlamydiae. Studies evaluating the ability of Chlamydia to infect, replicate, and survive in macrophages has produced conflicting results, mostly due to the use of various serovars and species as well as different infection readouts (Sun et al, 2012;Al-zeer et al, 2013;Datta et al, 2014;Lausen et al, 2018). Here we compared intracellular replication and inclusion development of serovars L2, D, and A in PMA stimulated THP-1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…LGV strains can infect mucosal surfaces but uniquely infect macrophages, causing an invasive sexually transmitted infection that disseminates to the regional draining lymph nodes (Lausen et al, 2018), although the adaptations that allow these strains to survive and proliferate in macrophages are mostly unknown. Infection with LGV isolates can cause genital ulcers, lymphadenopathy (buboes), fibrosis, and fistulae; ultimately resulting in damage to the mucosal epithelium and scarring (Rawla and Limaiem, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Chlamydia trachomatis Serovars Drive Differential Production of Proinflammatory Cytokines and Chemokines Depending on the Type of Cell Infected

Faris

Andersen

McCullough

et al. 2019

Front. Cell. Infect. Microbiol.

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Chlamydia trachomatis serovars A-C infect conjunctival epithelial cells and untreated infection can lead to blindness. D-K infect genital tract epithelial cells resulting in pelvic inflammatory disease, ectopic pregnancy, and sterility while L1-L3 infect epithelial cells and macrophages, causing an invasive infection. Despite some strains of Chlamydia sharing high nucleotide sequence similarity, the bacterial and host factors that govern tissue and cellular tropism remain largely unknown. Following introduction of C. trachomatis via intercourse, epithelial cells of the vagina, foreskin, and ectocervix are exposed to large numbers of the pathogen, yet their response to infection and the dynamics of chlamydial growth in these cells has not been well-characterized compared to growth in more permissive cell types that harbor C. trachomatis. We compared intracellular replication and inclusion development of representative C. trachomatis serovars in immortalized human conjunctival epithelial, urogenital epithelial, PMA stimulated THP-1 (macrophages), and HeLa cells. We demonstrate that urogenital epithelial cells of the vagina, ectocervix, and foreskin restrict replication of serovar A while promoting robust replication and inclusion development of serovar D and L2. Macrophages restrict serovars D and A while L2 proliferates in these cells. Furthermore, we show that GM-CSF, RANTES, GROα, IL-1α, IL-1β, IP-10, IL-8, and IL-18 are produced in a cell-type and serovar-specific manner. Collectively we have established a series of human cell lines that represent some of the first cell types to encounter C. trachomatis following exposure and show that differential production of key cytokines early during infection could regulate serovar-host cell specificity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Chlamydia trachomatis Serovars Drive Differential Production of Proinflammatory Cytokines and Chemokines Depending on the Type of Cell Infected

Faris

Andersen

McCullough

et al. 2019

Front. Cell. Infect. Microbiol.

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“…It is worth mentioning that, in vivo, the externalization of phosphatidylserine represents a key ‘eat me’ signal for the engulfment of apoptotic cells by phagocytes [36]. However, especially L chlamydial serovars can survive from intracellular elimination in macrophages, using them as Trojan horses for bacterial dissemination [37, 38].…”

Section: Discussionmentioning

confidence: 99%

Survival and death of intestinal cells infected by Chlamydia trachomatis

et al. 2019

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The sexually transmitted pathogen Chlamydia trachomatis (CT) is able to replicate and survive in human intestinal epithelial cells, being the gastro-intestinal tract a suitable site of residence for this microorganism. In this context, no detailed information about the mechanisms of cell death in intestinal cell lines after a chlamydial infection is available. The aim of this study was to compare the effect of two different CT serovars (D and L2) on the survival/death of different intestinal cell lines (Caco-2 and COLO-205), using endocervical cells (HeLa) as a reference model of genital infection. Seventy two hours after chlamydial infection at different multiplicity of infection (MOI) levels, the viability of HeLa, Caco-2 and COLO 205 cells was evaluated through dose-response experiments by means of a MTS-based assay. To get deeper insights in the mechanisms of cell death induced by CT, cell viability was assessed in presence of different inhibitors (i.e. pan-caspase inhibitor Z-VAD, necroptosis inhibitor Necrostatin-1, hydrogen peroxide scavenger catalase, caspase-1 inhibitor Ac-YVAD-cmk). Moreover, the activation of effector caspases and the presence of cellular apoptotic/necrotic changes were evaluated at different time points after CT infection. Our results demonstrated that, for both chlamydial serovars, intestinal cell lines are more resistant to CT-induced cell death compared to HeLa, thus representing a suitable ‘niche’ for chlamydial residence and replication. In literature, apoptosis has been widely described to be the main cell death mechanism elicited by chlamydia infection. However, our data demonstrate that necroptosis plays a relevant role, proceeding in parallel with apoptosis. The protective effect of catalase suggests the involvement of oxidative stress in triggering both cell death pathways. Moreover, we demonstrated that caspase-1 is involved in CT-induced cell death, potentially contributing to host inflammatory response and tissue damage. Cells infected by L2 serovar displayed a higher activation of effector caspases compared to cells infected with serovar D, suggesting a serovar-specific activation of apoptotic pathways and potentially explaining the greater virulence of L serovars. Finally, we found that Chlamydia elicits the early externalization of phosphatidylserine on the external leaflet of plasma membrane independently of caspase activation.

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“…During experimental genital infection with Chlamydia, there is recruitment of monocytes and macrophages to the genital tract which phagocytose and eliminate the pathogen intracellularly, limiting the development of disease. However, when intracellular killing is not effective, especially in M2 macrophages, bacteria can be easily disseminated to the lymphatic system and further replicate in the draining lymph nodes (Lausen et al, 2018;Tietzel et al, 2019).…”

Section: Chlamydia Sppmentioning

confidence: 99%

Cathepsins in Bacteria-Macrophage Interaction: Defenders or Victims of Circumstance?

Szulc-Dąbrowska

Bossowska-Nowicka

Struzik

et al. 2020

Front. Cell. Infect. Microbiol.

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Macrophages are the first encounters of invading bacteria and are responsible for engulfing and digesting pathogens through phagocytosis leading to initiation of the innate inflammatory response. Intracellular digestion occurs through a close relationship between phagocytic/endocytic and lysosomal pathways, in which proteolytic enzymes, such as cathepsins, are involved. The presence of cathepsins in the endo-lysosomal compartment permits direct interaction with and killing of bacteria, and may contribute to processing of bacterial antigens for presentation, an event necessary for the induction of antibacterial adaptive immune response. Therefore, it is not surprising that bacteria can control the expression and proteolytic activity of cathepsins, including their inhibitors – cystatins, to favor their own intracellular survival in macrophages. In this review, we summarize recent developments in defining the role of cathepsins in bacteria-macrophage interaction and describe important strategies engaged by bacteria to manipulate cathepsin expression and activity in macrophages. Particularly, we focus on specific bacterial species due to their clinical relevance to humans and animal health, i.e., Mycobacterium, Mycoplasma, Staphylococcus, Streptococcus, Salmonella, Shigella, Francisella, Chlamydia, Listeria, Brucella, Helicobacter, Neisseria, and other genera.

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Immunobiology of monocytes and macrophages during Chlamydia trachomatis infection

Cited by 22 publications

References 107 publications

Chlamydia trachomatis Serovars Drive Differential Production of Proinflammatory Cytokines and Chemokines Depending on the Type of Cell Infected

Chlamydia trachomatis Serovars Drive Differential Production of Proinflammatory Cytokines and Chemokines Depending on the Type of Cell Infected

Survival and death of intestinal cells infected by Chlamydia trachomatis

Cathepsins in Bacteria-Macrophage Interaction: Defenders or Victims of Circumstance?

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