Histopathologic patterns of female genital tuberculosis with clinical correlation: a 10-year (2013-2022) retrospective cross-sectional study.

OBJECTIVE: Underdiagnosis of female genital tuberculosis (FGTB) often leads to infertility. In this study, we aimed to determine the site and histopathologic patterns of FGTB and its correlation with clinical presentation and acid-fast bacilli (AFB) status. METHODS: A retrospective cross-sectional study was conducted on 122 patients with a histopathological diagnosis of FGTB at the Department of Pathology, College of Health Sciences (CHS), Tikur Anbessa Specialized Hospital (TASH), Addis Ababa University (AAU), from January 1, 2013, to August 30, 2022. RESULTS: Female genital tuberculosis was found in 0.94% of the gynecology specimens examined. The most common presentations were menstrual disturbance, abdominopelvic pain, and infertility. Among patients with FGTB, 4.6% exhibited misleading clinical and radiologic findings, leading to suspicion of malignancy and subsequent aggressive surgical management. The endometrium was the most frequently affected organ, followed by the fallopian tube, ovary, cervix, and vulva. In the majority of tuberculous endometritis cases (53.3%), histopathology revealed early-stage granulomas. Acid-fast bacilli were found in a significant proportion (42.6%) of FGTB tissues with TB histopathology. The ovary had the highest rate of AFB detection, followed by the fallopian tube, endometrium, and cervix. CONCLUSION: Female genital tuberculosis should be considered in reproductive-age women presenting with menstrual irregularities, abdominopelvic pain, infertility, or an abdominopelvic mass. The endometrium is commonly affected, displaying early granulomas with low AFB positivity.

Identification of differentially expressed genes and signaling pathways in human conjunctiva and reproductive tract infected with Chlamydia trachomatis.

BACKGROUND: Currently, Chlamydia trachomatis-specific host defense mechanisms in humans remain poorly defined. To study the characteristics of host cells infected early with Chlamydia trachomatis, we used bioinformatics methods to analyze the RNA transcription profiles of the conjunctiva, fallopian tubes, and endometrium in humans infected with Chlamydia trachomatis. METHOD: The gene expression profiles of GSE20430, GSE20436, GSE26692, and GSE41075 were downloaded from the Gene Expression Synthesis (GEO) database. Then, we obtained the differentially expressed genes (DEGs) through the R 4.0.1 software. STRING was used to construct protein-protein interaction (PPI) networks; then, the Cytoscape 3.7.2 software was used to visualize the PPI and screen hub genes. GraphPad Prism 8.0 software was used to verify the expression of the hub gene. In addition, the gene-miRNA interaction was constructed on the NetworkAnalyst 3.0 platform using the miRTarBase v8.0 database. RESULTS: A total of 600 and 135 DEGs were screened out in the conjunctival infection group and the reproductive tract infection group, respectively. After constructing a PPI network and verifying the hub genes, CSF2, CD40, and CSF3 in the reproductive tract infection group proved to have considerable statistical significance. CONCLUSION: In our research, the key genes in the biological process of reproductive tract infection with Chlamydia trachomatis were clarified through bioinformatics analysis. These hub genes may be further used in clinical treatment and clinical diagnosis.

Fallopian tubal infertility: the result of Chlamydia trachomatis-induced fallopian tubal fibrosis.

Chlamydia trachomatis is one of the most common pathogens of sexually transmitted diseases, and its incidence in genital tract infections is now 4.7% in south China. Infertility is the end result of C. trachomatis-induced fallopian tubal fibrosis and is receiving intense attention from scientists worldwide. To reduce the incidence of infertility, it is important to understand the pathology-related changes of the genital tract where C. trachomatis infection is significant, especially the mechanism of fibrosis formation. During fibrosis development, the fallopian tube becomes sticky and occluded, which will eventually lead to tubal infertility. At present, the mechanism of fallopian tubal fibrosis induced by C. trachomatis infection is unclear. Our study attempted to summarize the possible mechanisms of fibrosis caused by C. trachomatis infection in the fallopian tube by reviewing published studies and further providing potential therapeutic targets to reduce the occurrence of infertility. This study also provides ideas for future research. Factors leading to fallopian tube fibrosis include inflammatory factors, miRNA, ECT, cHSP, and host factors. We hypothesized that C. trachomatis mediates the transcription and translation of EMT and ECM via upregulating TGF signaling pathway, which leads to the formation of fallopian tube fibrosis and ultimately to tubal infertility.

Female Genital Tuberculosis: Clinical Presentation, Current Diagnosis, and Treatment.

Female genital tuberculosis is a disease caused by Mycobacterium tuberculosis infection in the female reproductive tract. The disease burden among women leads to infertility is significant, especially in developing countries. The bacteria can spread from the lung into the reproductive organ through lymphatic or hematogenous. Many patients present with atypical symptoms, which mimic other gynecological conditions. Several investigations are needed to establish the diagnosis. Almost all cases of genital TB affect the fallopian tube and cause infertility in patients and endometrial involvement. Current treatment still relies on antituberculosis therapy with a combination of tubal surgery. The present review describes the epidemiological data, clinical presentation, diagnosis, and currently available treatment to cure the disease and for in vitro fertilization.

Gonococcal Pelvic Inflammatory Disease: Placing Mechanistic Insights Into the Context of Clinical and Epidemiological Observations.

While infection by Neisseria gonorrhoeae is often asymptomatic in women, undetected infections can ascend into the upper genital tract to elicit an inflammatory response that manifests as pelvic inflammatory disease, with the outcomes depending on the intensity and duration of inflammation and whether it is localized to the endometrial, fallopian tube, ovarian, and/or other tissues. This review examines the contribution of N. gonorrhoeae versus other potential causes of pelvic inflammatory disease by considering new insights gained through molecular, immunological, and microbiome-based analyses, and the current epidemiological burden of infection, with an aim to highlighting key areas for future study.

The Impact of Selected Bacterial Sexually Transmitted Diseases on Pregnancy and Female Fertility.

Sexually transmitted infections (STIs) caused by Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium are a common cause of pelvic inflammatory disease (PID) which can lead to tubal factor infertility (TFI). TFI is one of the most common causes of infertility, accounting for 30% of female fertility problems. STIs can also have an impact on pregnancy, leading to adverse pregnancy outcomes. Escalating antibiotic resistance in Neisseria gonorrhoeae and Mycoplasma genitalium represents a significant problem and can be therapeutically challenging. We present a comprehensive review of the current treatment options, as well as the molecular approach to this subject. We have given special attention to molecular epidemiology, molecular diagnostics, current and new treatments, and drug resistance.

Toll-Like Receptor 3 Deficiency Leads to Altered Immune Responses to Chlamydia trachomatis Infection in Human Oviduct Epithelial Cells.

Reproductive tract pathology caused by Chlamydia trachomatis infection is an important global cause of human infertility. To better understand the mechanisms associated with Chlamydia-induced genital tract pathogenesis in humans, we used CRISPR genome editing to disrupt Toll-like receptor 3 (TLR3) function in the human oviduct epithelial (hOE) cell line OE-E6/E7 in order to investigate the possible role(s) of TLR3 signaling in the immune response to Chlamydia Disruption of TLR3 function in these cells significantly diminished the Chlamydia-induced synthesis of several inflammation biomarkers, including interferon beta (IFN-ß), interleukin-6 (IL-6), interleukin-6 receptor alpha (IL-6Rα), soluble interleukin-6 receptor beta (sIL-6Rß, or gp130), IL-8, IL-20, IL-26, IL-34, soluble tumor necrosis factor receptor 1 (sTNF-R1), tumor necrosis factor ligand superfamily member 13B (TNFSF13B), matrix metalloproteinase 1 (MMP-1), MMP-2, and MMP-3. In contrast, the Chlamydia-induced synthesis of CCL5, IL-29 (IFN-λ1), and IL-28A (IFN-λ2) was significantly increased in TLR3-deficient hOE cells compared to their wild-type counterparts. Our results indicate a role for TLR3 signaling in limiting the genital tract fibrosis, scarring, and chronic inflammation often associated with human chlamydial disease. Interestingly, we saw that Chlamydia infection induced the production of biomarkers associated with persistence, tumor metastasis, and autoimmunity, such as soluble CD163 (sCD163), chitinase-3-like protein 1, osteopontin, and pentraxin-3, in hOE cells; however, their expression levels were significantly dysregulated in TLR3-deficient hOE cells. Finally, we demonstrate using hOE cells that TLR3 deficiency resulted in an increased amount of chlamydial lipopolysaccharide (LPS) within Chlamydia inclusions, which is suggestive that TLR3 deficiency leads to enhanced chlamydial replication and possibly increased genital tract pathogenesis during human infection.

Influence of a mannose-binding lectin gene polymorphism and exposure to Chlamydia trachomatis on fallopian tube obstruction in Brazilian woman.

PURPOSE: Factors influencing fallopian tube occlusion in women with a lower genital tract infection remain incompletely elucidated. We evaluated whether a polymorphism in the mannose-binding lectin (MBL) gene at codon 54 influences the occurrence of fallopian tube blockage in relation to exposure to Chlamydia trachomatis. METHODS: In a case-control study at The Hospital das Clínicas, University of São Paulo, Brazil, 75 women with hysterosalpingography-documented tubal occlusion and 75 women with patent fallopian tubes were analyzed for detection of single-nucleotide polymorphism in codon 54 of the MBL gene and for IgG anti-C. trachomatis antibodies in their sera. Both groups were matched for age, race, and sexual variables. RESULTS: Prior exposure to C. trachomatis, as evidenced by the presence of IgG antibodies, was comparable in both groups. Detection of the polymorphic MBL allele was more prevalent in women with blocked tubes (p < 0.01), regardless of whether or not there was evidence of prior chlamydial exposure. CONCLUSION: The level of MBL-related innate immunity influences the consequences of infection by C. trachomatis or other microbes.

Bacterial Colonization of the Female Upper Genital Tract.

Bacteria colonize most of the human body, and the female genital tract is not an exception. While the existence of a vaginal microbiota has been well established, the upper genital tract has been considered a sterile environment, with a general assumption that bacterial presence is associated with adverse clinical manifestation. However, recent metagenomic studies identified specific patterns of microbiota colonizing the uterus, fallopian tubes, ovaries, and placenta. These results need confirmation and further investigations since the data are only scarce. Bacterial colonization of these sites appears different from the vaginal one, despite evidence that vaginal bacteria could ascend to the upper genital tract through the cervix. Are these bacteria only commensal or do they play a role in the physiology of the female upper genital tract? Which are the genera that may have a negative and a positive impact on the female reproductive function? The aim of this review is to critically present all available data on upper genital tract microbiota and discuss its role in human reproduction, ranging from the technical aspects of these types of analyses to the description of specific bacterial genera. Although still very limited, research focusing on genital colonization of bacteria other than the vaginal milieu might bring novel insights into physiopathology of human reproduction.

Impact of the Levonorgestrel-Releasing Intrauterine System on the Progression of Chlamydia trachomatis Infection to Pelvic Inflammatory Disease in a Baboon Model.

Background: Understanding the relationship between the levonorgestrel (LNG)-releasing intrauterine system (IUS) and sexually transmitted infections (STIs) is increasingly important as use of the LNG-IUS grows to include women at higher risk for STIs. This study assessed the impact of the LNG-IUS on development of Chlamydia trachomatis pelvic inflammatory disease, using a baboon model. Methods: Baboons with and those without the LNG-IUS were cervically inoculated with C. trachomatis and monitored daily, and cervical and fallopian tube swab specimens were collected weekly for C. trachomatis quantitation by nucleic acid amplification testing and culture. Vaginal swab specimens were collected for cytokine analysis, and serum samples were obtained for detection of C. trachomatis antibodies. Results: The LNG-IUS resulted in an increased C. trachomatis burden in the cervix, with the bacterial burden in the LNG-IUS group diverging from that in the non-LNG-IUS group by 6 weeks after infection. One of 7 baboons in the non-LNG-IUS group and 2 of 6 in the LNG-IUS group developed pelvic inflammatory disease, while 3 animals in each group met criteria suggestive of pelvic inflammatory disease. LNG-IUS increased baseline interleukin 8 levels but failed to further upregulate interleukin 8 during infection. In LNG-IUS recipients, early perturbations in the interleukin 1ß axis corresponded to decreased C. trachomatis clearance and increased T-helper type 2 immune responses. Conclusion: LNG-IUS use results in delayed clearance of C. trachomatis and might alter the reproductive tract immune environment.

Female genital tuberculosis: Revisited.

Female genital tuberculosis (FGTB) is caused by Mycobacterium tuberculosis (rarely Mycobacterium bovis and/or atypical mycobacteria) being usually secondary to TB of the lungs or other organs with infection reaching through haematogenous, lymphatic route or direct spread from abdominal TB. In FGTB, fallopian tubes are affected in 90 per cent women, whereas uterine endometrium is affected in 70 per cent and ovaries in about 25 per cent women. It causes menstrual dysfunction and infertility through the damage of genital organs. Some cases may be asymptomatic. Diagnosis is often made from proper history taking, meticulous clinical examination and judicious use of investigations, especially endometrial aspirate (or biopsy) and endoscopy. Treatment is through multi-drug antitubercular treatment for adequate time period (rifampicin, isoniazid, pyrazinamide, ethambutol daily for 60 days followed by rifampicin, isoniazid, ethambutol daily for 120 days). Treatment is given for 18-24 months using the second-line drugs for drug-resistant (DR) cases. With the advent of increased access to rapid diagnostics and newer drugs, the management protocol is moving towards achieving universal drug sensitivity testing and treatment with injection-free regimens containing newer drugs, especially for new and previously treated DR cases.

Genital tuberculosis in females.

The morbidity and mortality due to tuberculosis (TB) is high worldwide, and the burden of disease among women is significant, especially in developing countries. Mycobacterium tuberculosis bacilli reach the genital tract primarily by haematogenous spread and dissemination from foci outside the genitalia with lungs as the common primary focus. Genital TB in females is a chronic disease with low-grade symptoms. The fallopian tubes are affected in almost all cases of genital TB, and along with endometrial involvement, it causes infertility in patients. Many women present with atypical symptoms which mimic other gynaecological conditions. A combination of investigations is needed to establish the diagnosis of female genital TB (FGTB). Multidrug anti-TB treatment is the mainstay of management and surgery may be required in advanced cases. Conception rates are low among infertile women with genital TB even after multidrug therapy for TB, and the risk of complications such as ectopic pregnancy and miscarriage is high. More research is needed on the changing trends in the prevalence and on the appropriate methods for diagnosis of FGTB.

[THE STATE OF FALLOPIAN TUBES IN WOMEN WITH UROGENITAL CHLAMYDIA AND INFERTILITY].

The aim of this work was to assess the state of the fallopian tubes in women with urogenital chlamydia (UC) and infertility. 344 women 18-49 y.o with infertility have been investigated. UC was detected in 133 of them -38.7%, (main group), UC was absent in 211 (61.3%) patients (comparision group). In the main group prevailed the tubal or tubal peritoneal factor of infertility (51.9% versus 19.4% in the comparison group, p<0.001). UC in women in the main (62.4%) was in the form of mixed infection. Obstruction of the fallopian tubes and adhesions in the pelvic region were more often detected in patients of the main group (p<0.05). The most pronounced lesions of the fallopian tubes were observed in women with chlamydial mixed infection. Adhesive process in the small pelvis was established by laparascopy in 72.2% of women in the main group and in 27.8% in the comparison group (p<0.001). There was a correlation between the extent of the adhesion process in the small pelvis and the presence of chlamydial mixed infection. A histological study was carried out of the tissues of the fallopian tubes in 12 women diagnosed with an ectopic pregnancy, 5 of whom had UC. Women with UC have alternating areas with signs of acute inflammation and various stages of the reparative processand in 4 women with UC the above mentioned signs and sclerosis were detected also in the the submucosa, which can cause destruction of the functional activities of the fallopian tubes and obstruction as well. All this causes a violation of the transport of spermatozoa, the embryo and leads to a ectopic pregnancy and infertility. Obtained results explain the inefficiency of restoring reproductive function in women after elimination of UC with preserved patency of the fallopian tubes.

The Chromosome-Encoded Hypothetical Protein TC0668 Is an Upper Genital Tract Pathogenicity Factor of Chlamydia muridarum.

We previously associated a missense mutation of the tc0668 gene of serial in vitro-passaged Chlamydia muridarum, a murine model of human urogenital C. trachomatis, with severely attenuated disease development in the upper genital tract of female mice. Since these mutants also contained a TC0237 Q117E missense mutation that enhances their in vitro infectivity, an effort was made here to isolate and characterize a tc0668 single mutant to determine its individual contribution to urogenital pathogenicity. Detailed genetic analysis of C. muridarum passages revealed a truncated variant with a G216* nonsense mutation of the 408-amino-acid TC0668 protein that does not produce a detectable product. Intracellular growth and infectivity of C. muridarum in vitro remain unaffected in the absence of TC0668. Intravaginal inoculation of the TC0668 null mutant into C3H/HeJ mice results in a typical course of lower genital tract infection but, unlike a pathogenic isogenic control, is unable to elicit significant chronic inflammation of the oviduct and fails to induce hydrosalpinx. Thus, TC0668 is demonstrated as an important chromosome-encoded urogenital pathogenicity factor of C. muridarum and the first with these characteristics to be discovered for a Chlamydia pathogen.

Role of Chlamydia trachomatis and emerging Chlamydia-related bacteria in ectopic pregnancy in Vietnam.

In this case-control study, we investigated the seroprevalence and molecular evidence of Chlamydia trachomatis and Waddlia chondrophila in ectopic pregnancies (EP) and uneventful control pregnancies in 343 women from Vietnam. Whereas presence of C. trachomatis IgG was strongly associated with EP [adjusted odds ratio (aOR) 5·41, 95% confidence interval (CI) 2·58-11·32], its DNA remained undetected in all tubal lesions. We confirmed an independent association between antibodies against Waddlia and previous miscarriage (aOR 1·87, 95% CI 1·02-3·42). Further investigations are needed to understand the clinical significance of Waddlia's high seroprevalence (25·9% in control pregnancies) in this urban population.

Prevalence of 7 sexually transmitted organisms by multiplex real-time PCR in Fallopian tube specimens collected from Saudi women with and without ectopic pregnancy.

BACKGROUND: Ectopic pregnancy (EP) is associated with maternal morbidity and occasionally mortality during the first trimester. A history of sexually transmitted infection (STI) and pelvic inflammatory disease have been implicated as major risk factors for EP. Our aim was to measure the prevalence of Chlamydia trachomatis (CT), Neisseria gonorrhoeae, Mycoplasma genitalium (MG), Ureaplasma parvum/urealyticum, Gardnerella vaginalis, Trichomonas vaginalis and herpes simplex virus (HSV)-1&2 in Fallopian tubes collected from EP and the results were compared with those obtained from total abdominal hysterectomy (TAH) and tubal ligation. METHODS: This was a prospective case-control study and tubal samples were collected from 135 Saudi women recruited from 3 centres in the Western region as follow: 84 EPs, 20 TAH and 31 tubal ligations. Multiplex TaqMan PCR was performed using an IVD CE kit for the simultaneous detection of candidate pathogens following DNA extraction. RESULTS: Infections were detected in 31.8 % of the 135 participants either as single (11.1 %) or co-infections (20.7 %) and the frequencies were significantly higher in EP (42.85 %) compared with control (13.72 %). The rates of CT (27.4 %; P = 0.001); MG (20.2 %; P = 0.009) and HSV-1/2 (21.4 %; P = 0.01) were significantly higher in EP. No significant difference between the study groups was observed for the other pathogens (P > 0.05). Binary logistic regression also showed that infection with ≥ 2 pathogens (OR 4.9; 95 % CI: 2.2 - 11.6; P = 0.006), CT (OR 3.07; 95 % CI: 1.3 - 12.3; P = 0.002), MG (OR 2.3; 95 % CI: 1.1 - 8.6; P = 0.03) and HSV-1/2 (OR 1.7; 95 % CI: 0.75 - 5.7; P = 0.004) were associated with a significantly higher risk of developing EP. CONCLUSIONS: STIs are frequent in the upper genital tract of Saudi women during the reproductive age and, CT, MG and HSV-1/2 were more prevalent in EP. The observed high rates of co-infection advocate the necessity of establishing national guidelines and/or screening program utilising multiplex PCR approach for the detection of common STIs among high risk groups in the kingdom. Further studies are needed to measure the adverse reproductive outcomes associated with STIs in Saudi Arabia.

Lack of long-lasting hydrosalpinx in A/J mice correlates with rapid but transient chlamydial ascension and neutrophil recruitment in the oviduct following intravaginal inoculation with Chlamydia muridarum.

Lower genital tract infection with Chlamydia trachomatis and C. muridarum can induce long-lasting hydrosalpinx in the upper genital tract of women and female mice, respectively. However, A/J mice were highly resistant to induction of long-lasting hydrosalpinx by C. muridarum. We further compared host inflammatory responses and chlamydial infection courses between the hydrosalpinx-resistant A/J mice and CBA/J mice known to be susceptible to hydrosalpinx induction. Both mouse strains developed robust pyosalpinx during the acute phase followed by hydrosalpinx during the chronic phase. However, the hydrosalpinges disappeared in A/J mice by day 60 after infection, suggesting that some early hydrosalpinges are reversible. Although the overall inflammatory responses were indistinguishable between CBA/J and A/J mice, we found significantly more neutrophils in oviduct lumen of A/J mice on days 7 and 10, which correlated with a rapid but transient oviduct invasion by C. muridarum with a peak infection on day 7. In contrast, CBA/J mice developed a delayed and extensive oviduct infection. These comparisons have revealed an important role of the interactions of oviduct infection with inflammatory responses in chlamydial induction of long-lasting hydrosalpinx, suggesting that a rapid but transient invasion of oviduct by chlamydial organisms can prevent the development of the long-lasting hydrosalpinges.

Vaginal Bacteria Elicit Acute Inflammatory Response in Fallopian Tube Organoids.

To facilitate in vitro mechanistic studies in pelvic inflammatory disease and subsequent tubal factor infertility, we sought to establish patient tissue derived fallopian tube (FT) organoids and to study their inflammatory response to acute vaginal bacterial infection. FT tissues were obtained from four patients after salpingectomy for benign gynecological diseases. We introduced acute infection in the FT organoid culture system by inoculating the organoid culture media with two common vaginal bacterial species, Lactobacillus crispatus and Fannyhessea vaginae. The inflammatory response elicited in the organoids after acute bacterial infection was analyzed by the expression profile of 249 inflammatory genes. Compared to the negative controls that were not cultured with any bacteria, the organoids cultured with either bacterial species showed multiple differentially expressed inflammatory genes. Marked differences were noted between the Lactobacillus crispatus infected organoids and those infected by Fannyhessea vaginae. Genes from the C-X-C motif chemokine ligand (CXCL) family were highly upregulated in Fannyhessea vaginae infected organoids. Flow cytometry showed that immune cells quickly disappeared during the organoid culture, indicating the inflammatory response observed with bacterial culture was generated by the epithelial cells in the organoids. In summary, we have shown that patient tissue derived FT organoids respond to acute bacterial infection with upregulation of inflammatory genes specific to different vaginal bacterial species. FT organoids is a useful in vitro model system to study the host-pathogen interaction during bacterial infection.

IL-17C is a driver of damaging inflammation during Neisseria gonorrhoeae infection of human Fallopian tube.

The human pathogen Neisseria gonorrhoeae ascends into the upper female reproductive tract to cause damaging inflammation within the Fallopian tubes and pelvic inflammatory disease (PID), increasing the risk of infertility and ectopic pregnancy. The loss of ciliated cells from the epithelium is thought to be both a consequence of inflammation and a cause of adverse sequelae. However, the links between infection, inflammation, and ciliated cell extrusion remain unresolved. With the use of ex vivo cultures of human Fallopian tube paired with RNA sequencing we defined the tissue response to gonococcal challenge, identifying cytokine, chemokine, cell adhesion, and apoptosis related transcripts not previously recognized as potentiators of gonococcal PID. Unexpectedly, IL-17C was one of the most highly induced genes. Yet, this cytokine has no previous association with gonococcal infection nor pelvic inflammatory disease and thus it was selected for further characterization. We show that human Fallopian tubes express the IL-17C receptor on the epithelial surface and that treatment with purified IL-17C induces pro-inflammatory cytokine secretion in addition to sloughing of the epithelium and generalized tissue damage. These results demonstrate a previously unrecognized but critical role of IL-17C in the damaging inflammation induced by gonococci in a human explant model of PID.

Peptidoglycan fragment release from Neisseria meningitidis.

Neisseria meningitidis (meningococcus) is a symbiont of the human nasopharynx. On occasion, meningococci disseminate from the nasopharynx to cause invasive disease. Previous work showed that purified meningococcal peptidoglycan (PG) stimulates human Nod1, which leads to activation of NF-κB and production of inflammatory cytokines. No studies have determined if meningococci release PG or activate Nod1 during infection. The closely related pathogen Neisseria gonorrhoeae releases PG fragments during normal growth. These fragments induce inflammatory cytokine production and ciliated cell death in human fallopian tubes. We determined that meningococci also release PG fragments during growth, including fragments known to induce inflammation. We found that N. meningitidis recycles PG fragments via the selective permease AmpG and that meningococcal PG recycling is more efficient than gonococcal PG recycling. Comparison of PG fragment release from N. meningitidis and N. gonorrhoeae showed that meningococci release less of the proinflammatory PG monomers than gonococci and degrade PG to smaller fragments. The decreased release of PG monomers by N. meningitidis relative to N. gonorrhoeae is partly due to ampG, since replacement of gonococcal ampG with the meningococcal allele reduced PG monomer release. Released PG fragments in meningococcal supernatants induced significantly less Nod1-dependent NF-κB activity than released fragments in gonococcal supernatants and tended to induce less interleukin-8 (IL-8) secretion in primary human fallopian tube explants. These results support a model in which efficient PG recycling and extensive degradation of PG fragments lessen inflammatory responses and may be advantageous for maintaining meningococcal carriage in the nasopharynx.