TRIM32 reduced the recruitment of innate immune cells and the killing capacity of Listeria monocytogenes by inhibiting secretion of chemokines.

Listeria monocytogenes (Lm) is a facultative, intracellular Gram-positive pathogenic bacterium that causes sepsis, a condition characterized by persistent excessive inflammation and organ dysfunction. However, the pathogenesis of Lm-induced sepsis is unknown. In this research, we discovered that TRIM32 is required for innate immune regulation during Lm infection. Trim32 deficiency remarkably reduced bacteremia and proinflammatory cytokine secretion in mice with severe Lm infection, preventing sepsis. Trim32-/- mice had a lower bacterial burden after Lm infection and survived significantly longer than wild-type (WT) mice, as well as lower serum levels of inflammatory cytokines TNF-α, IL-6, IL-18, IL-12p70, IFN-ß, and IFN-γ at 1 day post infection (dpi) compared to WT mice. On the other hand, the chemokines CXCL1, CCL2, CCL7, and CCL5 were enhanced at 3 dpi in Trim32-/- mice than WT mice, reflecting increased recruitment of neutrophils and macrophages. Furthermore, Trim32-/- mice had higher levels of macrophage-associated iNOS to kill Lm. Collectively, our findings suggest that TRIM32 reduces innate immune cells recruitment and Lm killing capabilities via iNOS production.

Maternal bacteremia caused by Listeria monocytogenes ST87: A case report.

Pregnant women are at a high risk of contracting listeriosis; however, there have been only a few clinical reports of maternal bacteremia occurring before 20 weeks of gestation in China. In this case report, a 28-year-old pregnant woman at 16 weeks and 4 days of gestation was admitted to our hospital suffering from fever for four days. The patient was initially diagnosed with an upper respiratory tract infection at the local community hospital; nevertheless, the cause of the infection was unknown. In our hospital, she was diagnosed with Listeria monocytogenes (L. monocytogenes) infection by the blood culture system. Before the results of blood culture were obtained, ceftriaxone and cefazolin were given for three days respectively based on clinical experience. However, the fever didn't reduce until she was treated with ampicillin. This pathogen was further identified as L. monocytogenes ST87 by serotyping, multilocus sequence typing (MLST), and virulence gene amplification. Finally, a healthy baby boy was born in our hospital, and the neonate was developing well at the 6-week postnatal follow-up visit. This case report suggests that patients with L. monocytogenes ST87-caused maternal listeriosis can have a good prognosis; however, more clinical information and molecular experiments are needed to confirm our hypothesis.

Need for more robust research on the effectiveness of masks in preventing COVID-19 transmission.

The COVID-19 pandemic has caused dramatic death and infection worldwide, leading to a global public health crisis. As for precautions, scientists have different opinions on the effectiveness of masks in preventing COVID-19 transmission. Published studies suggested that medical masks may help in preventing respiratory virus infection. But the currently available experimental results are too preliminary to support an informed policy. In conclusion, we need more well-designed and robust research on the effectiveness of masks in preventing COVID-19 infection.

Increased systemic RNA oxidative damage and diagnostic value of RNA oxidative metabolites during Shigella flexneri-induced intestinal infection.

BACKGROUND: Shigella flexneri (S. flexneri) is a major pathogen causing acute intestinal infection, but the systematic oxidative damage incurred during the course of infection has not been investigated. AIM: To investigate the incurred systemic RNA oxidative damage and the diagnostic value of RNA oxidative metabolites during S. flexneri-induced intestinal infection. METHODS: In this study, a Sprague-Dawley rat model of acute intestinal infection was established by oral gavage with S. flexneri strains. The changes in white blood cells (WBCs) and cytokine levels in blood and the inflammatory response in the colon were investigated. We also detected the RNA and DNA oxidation in urine and tissues. RESULTS: S. flexneri infection induced an increase in WBCs, C-reactive protein, interleukin (IL)-6, IL-10, IL-1ß, IL-4, IL-17a, IL-10, and tumor necrosis factor α (TNF-α) in blood. Of note, a significant increase in urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn), an important marker of total RNA oxidation, was detected after intestinal infection (P = 0.03). The urinary 8-oxo-Gsn level returned to the baseline level after recovery from infection. In addition, the results of a correlation analysis showed that urinary 8-oxo-Gsn was positively correlated with the WBC count and the cytokines IL-6, TNF-α, IL-10, IL-1ß, and IL-17α. Further detection of the oxidation in different tissues showed that S. flexneri infection induced RNA oxidative damage in the colon, ileum, liver, spleen, and brain. CONCLUSION: Acute infection induced by S. flexneri causes increased RNA oxidative damage in various tissues (liver, spleen, and brain) and an increase of 8-oxo-Gsn, a urinary metabolite. Urinary 8-oxo-Gsn may be useful as a biomarker for evaluating the severity and prognosis of infection.

Downregulation of GSK3B by miR-132-3p Enhances Etoposide-Induced Breast Cancer Cell Apoptosis.

OBJECTIVE: MicroRNAs (miRNAs) have been confirmed to play an essential role in modulating cancer cell proliferation, metastasis, and sensitivity to chemotherapy. However, the correlation between miR-132-3p expression and etoposide (VP16) induced apoptosis in human breast cancer cells remains poorly understood. METHODS: Six datasets, including three gene expression profile datasets and three microRNA (miRNA) expression profile datasets, were downloaded from the NCBI Gene Expression Omnibus (GEO) database to identify miR-132-3p and GSK3B expression in breast cancer. Kaplan-Meier and log-rank testing were performed to evaluate the effect of miR-132-3p and GSK3B on the survival of breast cancer. Flow cytometry analysis was used to determine the effects of miR-132-3p and GSK3B on breast cancer cell apoptosis. Luciferase reporter assay, Western blot, and real-time PCR were used to determine the regulatory effect of miR-132-3p on GSK3B. RESULTS: miR-132-3p was significantly downregulated in breast cancer tissues compared with normal breast epithelial cells, whereas GSK3B expression was remarkably over-expressed in breast cancer tissues. The patients with low miR-132-3p or high GSK3B expression had worse overall survival. Luciferase reporter assay, Western blot, and real-time PCR confirmed that miR-132-3p could inhibit GSK3B protein and mRNA expression via binding to the 3'-UTR of GSK3B. Furthermore, miR-132-3p enhanced VP16-induced breast cancer cell apoptosis through targeting GSK3B. CONCLUSION: Collectively, the results of this study indicated that miR-132-3p was downregulated in breast cancer tissues and directly targeted GSK3B to be implicated in the modulation of breast cancer cell apoptosis, suggesting that miR-132-3p/GSK3B might be a novel, effective therapeutic target for treating patients with breast cancer.

The influence of hepatitis B virus infection in pregnant women.

We carried out the investigation to evaluate hepatitis B virus (HBV) infection status and the influence of HBV infection in pregnant women in Tianjin of China. We founded that the prevalence of HBsAg was 3.77% (69/1829). 88.57% (1620/1829) pregnant women conducted HBsAg screening in last pregnancy. Spontaneous abortion and premature delivery did not show significant differences between HBV infected and uninfected pregnant women. But ALT and AST levels were significantly higher in infected women. And 56.65% of participants (997/1760) were anti-HBs positive. In conclusion, HBsAg prevalence was moderate in pregnant women in this region, which was consistent with the total population in western Pacific regions. And HBV infection did not influence spontaneous abortion and premature delivery. But the HBsAg screening was conducted mostly in the last pregnancy. Early screening and intervention were suggested in pregnant women within countries of moderately endemic regions.

Systemic RNA oxidation can be used as a biomarker of infection in challenged with Vibrio parahaemolyticus.

More and more evidence support the concept that RNA oxidation plays a substantial role in the progress of multiple diseases; however, only a few studies have reported RNA oxidation caused by microbial pathogens. Urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn), which are broadly used as indicators of oxidative damage of RNA and DNA, were analyzed in this study to determine which can be used as a biomarker of infection in challenged with Vibrio parahaemolyticus (V. parahaemolyticus). In this work, 24 specific-pathogen-free (SPF) male SD rats were randomly divided into two groups: an infection group and a phosphate-buffered saline (PBS) control group. Our results proved that 8-oxo-Gsn rather than 8-oxo-dGsn was significantly increased after challenged with V. parahaemolyticus in urine and tissue samples of SD rats compared with the PBS control group. Simultaneously, white blood cells (WBCs) counts, intestinal inflammation and inflammatory factors (including CRP, IL-6, IL-1ß, TNF-α, IL-10, and IL-17A) were also increased sharply. Which has more clinical value is that the trend of urinary 8-oxo-Gsn was consistent with WBCs, intestinal inflammation and all kinds of inflammatory factors. More importantly is that urinary 8-oxo-Gsn of infection group was positively correlated with WBCs and various inflammatory cytokines. In a word, our results demonstrated that as a systemic RNA oxidation biomarker, we hope 8-oxo-Gsn can be used as a biomarker of the severity of microbial pathogens infection, rather than a specific biomarker of microbial pathogens infection.

Type 3 Innate Lymphoid Cells Direct Goblet Cell Differentiation via the LT-LTßR Pathway during Listeria Infection.

As a specialized subset of intestinal epithelial cells (IECs), goblet cells (GCs) play an important role during the antibacterial response via mucin production. However, the regulatory mechanisms involved in GC differentiation and function during infection, particularly the role of immune cell-IEC cross-talk, remain largely unknown. In this study, using Villin∆Ltbr conditional knockout mice, we demonstrate that LTßR, expressed on IECs, is required for GC hyperplasia and mucin 2 (MUC2) expression during Listeria infection for host defense but not homeostatic maintenance in the naive state. Analysis of single gene-deficient mice revealed that the ligand lymphotoxin (LT), but not LIGHT, and type 3 innate lymphoid cells (ILC3s), but not conventional T cells, are required for MUC2-dependent Listeria control. Conditional deficiency of LT in ILC3s further confirmed the importance of LT signals derived from ILC3s. Lack of ILC3-derived LT or IEC-derived LTßR resulted in the defective expression of genes related to GC differentiation but was not correlated with IEC proliferation and cell death, which were found to be normal by Ki-67 and Annexin V staining. In addition, the alternative NF-κB signaling pathway (involving RelB) in IECs was found to be required for the expression of GC differentiation-related genes and Muc2 and required for the anti-Listeria response. Therefore, our data together suggest a previously unrecognized ILC3-IEC interaction and LT-LTßR-RelB signaling axis governing GC differentiation and function during Listeria infection for host defense.

Oxidative DNA and RNA damage and their prognostic values during Salmonella enteritidis-induced intestinal infection in rats.

Emerging evidence suggests that microbial pathogens may induce oxidative stress in infected hosts. The aim of the present study was to investigate the relationship between changes in oxidative stress and intestinal infection with and without antibiotic treatment in animal models. Sprague-Dawley (SD) rats were divided into three groups: rats infected with Salmonella enterica serovar Enteritidis (S. enteritidis), rats infected with S. enteritidis followed by norfloxacin treatment, and the control group. To evaluate oxidative stress changes, levels of 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dGsn), which represented oxidative damage to RNA and DNA, respectively, were analysed in urine and tissue samples. In urine, the level of 8-oxo-Gsn increased significantly after oral exposure to S. enteritidis (p ≤ 0.001) and returned to baseline after recovery. Notably, norfloxacin treatment decreased the level of 8-oxo-Gsn in urine significantly (p = 0.001). Changes of 8-oxo-Gsn measured in tissues from the small intestine, colon, liver and spleen were consistent with 8-oxo-Gsn measured in urine. Our study suggested that 8-oxo-Gsn in urine may serve as a highly sensitive biomarker for evaluating the severity of S. enteritidis infection and the effectiveness of antibiotic treatment against infection.

Phenol-soluble modulin α4 mediates Staphylococcus aureus-associated vascular leakage by stimulating heparin-binding protein release from neutrophils.

Vascular leakage frequently occurs in patients with severe Staphylococcus aureus infection. However, the mechanism underlying S. aureus infection-induced vascular leakage remains unclear. Here, we identified the S. aureus virulence factor phenol-soluble modulin (PSM)α4 from the culture supernatant of strain USA300 as a stimulator of heparin-binding protein (HBP) release from polymorphonuclear neutrophils (PMNs) and demonstrated that PSMα4-induced HBP release from PMNs leads to vascular leakage. PSMα4 appeared less cytolytic than PSMα1-3 and was insensitive to lipoproteins; it significantly increased myeloperoxidase and elastase release from PMNs and cell surface CD63 expression in PMNs. PSMα4-induced HBP release required formyl peptide receptor 2 (FPR2) and phosphoinositide 3-kinase (PI3K) and depended on Ca(2+) influx and cytoskeleton rearrangement. Thus, PSMα4 may stimulate HBP release by activating FPR2 and PI3K to initiate PMN degranulation. PSMα4-induced HBP release from PMNs increased endothelial cell monolayer permeability in vitro and induced vascular leakage in mice. This novel function of PSMα4 may contribute to the pathogenesis of S. aureus and may be a potential therapeutic target.

Binding of Human Fibrinogen to MRP Enhances Streptococcus suis Survival in Host Blood in a αXß2 Integrin-dependent Manner.

The Gram-positive bacterium Streptococcus suis serotype 2 (S. suis 2), an important zoonotic pathogen, induces strong systemic infections in humans; sepsis and meningitis are the most common clinical manifestations and are often accompanied by bacteremia. However, the mechanisms of S. suis 2 survival in human blood are not well understood. In our previous study, we identified muramidase-released protein (MRP), a novel human fibrinogen (hFg)-binding protein (FBP) in S. suis 2 that is an important epidemic infection marker with an unknown mechanism in pathogenesis. The present study demonstrates that the N-terminus of MRP (a.a. 283-721) binds to both the Aα and Bß chains of the D fragment of hFg. Strikingly, the hFg-MRP interaction improved the survival of S. suis 2 in human blood and led to the aggregation and exhaustion of polymorphonuclear neutrophils (PMNs) via an αXß2 integrin-dependent mechanism. Other Fg-binding proteins, such as M1 (GAS) and FOG (GGS), also induced PMNs aggregation; however, the mechanisms of these FBP-hFg complexes in the evasion of PMN-mediated innate immunity remain unclear. MRP is conserved across highly virulent strains in Europe and Asia, and these data shed new light on the function of MRP in S. suis pathogenesis.

Preliminary investigation of human serum albumin-Vß inhibition on toxic shock syndrome induced by staphylococcus enterotoxin B in vitro and in vivo.

Staphylococcus enterotoxin B (SEB) is a superantigen that can induce massive activation of T cells with specific Vß and inflammatory cytokine cascades, which mediate shock. To date, no SEB vaccine has been developed for preventing toxic shock syndrome (TSS). Here, we evaluated the therapeutic effect of a fusion protein human serum albumin-Vß (HSA-Vß) on TSS induced by SEB. Compared with Vß, the preparation of HSA-Vß was much easier to handle owing to its solubility. Affinity testing showed that HSA-Vß had high affinity for SEB. In vitro results showed that HSA-Vß could effectively inhibit interferon (IFN)-γ and tumor necrosis factor (TNF)-α secretion by human peripheral blood mononuclear cells. Moreover, in vivo, HSA-Vß reduced IFN-γ and TNF-α levels in the serum and protected mice from SEB lethal challenge when administered simultaneously with SEB or 30 min after SEB. In summary, we simplified the preparation of Vß by fusion with HSA, creating the HSA-Vß protein, which effectively inhibited cytokine production and protected mice from lethal challenge with SEB. These data indicated that HSA-Vß may represent a novel therapeutic strategy for the treatment of SEB-induced TSS.

[Correlation between Type IV secretion system component VirD4 and virulence for Streptococcus suis 2].

OBJECTIVE: In order to study the role of SS2 Type IV Secretion System VirD4 in evasion of the host innate immune killing, we constructed a knockout mutant AVirD4. Then we studied its biological activity and virulence. METHODS: The two VirD4 flanking DNA sequences were amplified using genome of 05ZYH33 as template. We also amplified the Cm sequence of shuttle vector pSET1, and through overlap extension PCR we connected the three fragments together. Using suicide vector pSET4s, we constructed the recombinant gene knockout vector pSET4s::VirD4. The mutant AVirD4 was successfully constructed by allelic replacement. Virulence of mutant strain was compared with wild type strain 05ZYH33 through in vitro bactericidal assays, competitive infection and challenge experiment of CD1 mice. RESULTS: Mutant strain AVirD4 was constructed successfully, its virulence attenuated compared to the wild type strain. CONCLUSION: These findings indicated that Type IV Secretion System component VirD4 contributed to the virulence of S. suis with important functions in evading innate immunocyte killing.

Toll-like receptor 4 confers inflammatory response to Suilysin.

Streptococcus suis serotype 2 (SS2) is an emerging human pathogen worldwide. A large outbreak occurred in the summer of 2005 in China. Serum samples from this outbreak revealed that levels of the main proinflammatory cytokines were significantly higher in patients with streptococcal toxic-shock-like syndrome (STSLS) than in patients with meningitis only. However, the mechanism underlying the cytokine storm in STSLS caused by SS2 remained unclear. In this study, we found that suilysin (SLY) is the main protein inflammatory stimulus of SS2 and that native SLY (nSLY) stimulated cytokines independently of its haemolytic ability. Interestingly, a small amount of SLY (Å Mol/L) induced strong, long-term TNF-α release from human PBMCs. We also found that nSLY stimulated TNF-α in wild-type macrophages but not in macrophages from mice that carried a spontaneous mutation in TLR4 (P712H). We demonstrated for the first time that SLY stimulates immune cells through TLR4. In addition, the Myd88 adaptor-p38-MAPK pathway was involved in this process. The present study suggested that the TLR4-dependent inflammatory responses induced by SLY in host might contribute to the STSLS caused by SS2 and that p38-MAPK could be used as a target to control the release of excess TNF-α induced by SS2.

Functional and Structural Characterization of the Antiphagocytic Properties of a Novel Transglutaminase from Streptococcus suis.

Streptococcus suis serotype 2 (Ss2) is an important swine and human zoonotic pathogen. In the present study, we identified a novel secreted immunogenic protein, SsTGase, containing a highly conserved eukaryotic-like transglutaminase (TGase) domain at the N terminus. We found that inactivation of SsTGase significantly reduced the virulence of Ss2 in a pig infection model and impaired its antiphagocytosis in human blood. We further solved the crystal structure of the N-terminal portion of the protein in homodimer form at 2.1 Å. Structure-based mutagenesis and biochemical studies suggested that disruption of the homodimer directly resulted in the loss of its TGase activity and antiphagocytic ability. Characterization of SsTGase as a novel virulence factor of Ss2 by acting as a TGase would be beneficial for developing new therapeutic agents against Ss2 infections.

Proteomics identification of novel fibrinogen-binding proteins of Streptococcus suis contributing to antiphagocytosis.

Streptococcus suis serotype 2 (SS2) induced sepsis and meningitis are often accompanied by bacteremia. However, the mechanism whereby it helps S. suis to evade PMN-mediated phagocytosis remain unclear. Because of the central roles of bacteria-human fibrinogen (hFg) interaction in innate immunity, here, a proteomics based Far-western blotting (PBFWB) was developed to identify the fibrinogen-binding surface proteins of S. suis (SsFBPs) on a large-scale. And then thirteen potential SsFBPs were identified by PBFWB and we selected seven potential surface proteins to further confirm their binding ability to hFg, of which the gene mutant strains of MRP displayed significantly decrease in binding to immobilized hFg. Additionally, the polyclonal antibodies against Enolase were found to significantly inhibit the binding of SS2 to hFg. Strikingly, MRP and Enolase were found to improve the antiphagocytic ability of SS2 to PMNs by interacting with hFg and enhance the survival of SS2 in human blood. Taken together, the PBFWB method provides useful clues to the bacteria-host interactions. These studies firstly disclose MRP and Enolase were involved in immune evasion of SS2 at least in part by binding to Fg, which make them potential targets for therapies for SS2 infection.

Increased production of suilysin contributes to invasive infection of the Streptococcus suis strain 05ZYH33.

Streptococcus suis serotype 2 (SS2) is widely recognized in the veterinary world as the cause of rapidly progressive and fatal sepsis in infant pigs, manifested with meningitis, polyarthritis and pneumonia. It has evolved into a highly infectious strain, and caused two large-scale outbreaks of human epidemic in China, characterized bytypical toxic-shock syndrome and invasive infection. However, the molecular basis of virulence of this emerging zoonotic pathogen is still largely unknown. The present study shows that the sequence type (ST)7 epidemic strain S. suis 05ZYH33 causes higher mortality, higher necrosis of polymorphonuclear neutrophils and a significantly higher damage to human umbilical vein endothelial cells compared to the non-epidemic strain S. suis 1940. These differences appear to associate with the enhanced secretion of suilysin (sly) by S. suis 05ZYH33 compared to the non-epidemic strain 1940. Inclusion of additional strains confirmed that the epidemic ST7 strains produce more sly protein (mean, 1.49 g/ml; range, 0.76­1.91 g/ml) than non­epidemic strains (mean, 0.33 g/ml; range, 0.07-0.94 g/ml), and this difference is significant (P<0.001). The nonpolar mutant strain S. suis Δsly, constructed from the epidemic ST7 strain S. suis 05ZYH33 confirmed the role of sly on the enhanced virulence of S. suis ST7 strains. These findings suggest that increased sly production in S. suis 05ZYH33 facilitates penetration to the epithelium and its survival in the bloodstream, thereby contributing to the invasive infection.

[Expression, purification and hIgG-binding activity identification of truncated Streptococcus suis factor H-binding protein].

OBJECTIVE: To construct a prokaryotic expression vector of the His-tagged truncated factor H-binding protein (Fhb) fragments, Fhb-N (amino acids 45-344aa) and Fhb-C (amino acids 345-644aa), of Streptococcus suis serotype 2, express it in E.coli BL21 (DE3) in order to acquire high-purity recombinant protein, and finally identify the binding activity with human serum IgG (hIgG). METHODS: Fhb-N gene and Fhb-C gene were amplified using the primers designed according to 05ZYH33 genome sequences and cloned into the expression vector pET28a⁺ to construct recombinant plasmids. The plasmids were transformed into E.coli BL21 (DE3) and induced to express by IPTG. The recombinant proteins were purified by nickel affinity chromatography and identified by Western blotting. The hIgG was purified from human serum by HiTrap protein G HP column in accordance with the manufacturer's instructions. In addition, the specific binding to hIgG was identified by Western blotting and biolayer Interferometry (BLI). RESULTS: The prokaryotic expression vector of His-Fhb-N and His-Fhb-C was constructed, and the target proteins were expressed, purified and identified. The specific binding activity with hIgG was identified and the binding region was found located on the Fhb-N(45-344aa). CONCLUSION: His-Fhb-N can specifically bind to hIgG, which will help us to further study the role of Fhb-hIgG interaction in the pathogenesis of Streptococcus suis.

Streptococcus suis adenosine synthase functions as an effector in evasion of PMN-mediated innate immunit.

Streptococcus suis serotype 2 (S. suis 2) is a highly invasive pathogen in pigs and humans that can cause severe systemic infection. Sepsis and meningitis are the most common clinical manifestations of S. suis 2 infection. However, the mechanisms of S. suis 2 surviving in human blood remains unclear, so to identify novel virulence factors in evasion of polymorphonuclear leukocyte (PMN)-mediated innate immunity play important roles in developing therapies against S. suis 2 infection. Here, we found that S. suis 2 can escape phagocytic clearance by adenosine synthesis in blood. Through bioinformatics-based analyses we identified a cell wall-anchored protein harbors a 5'-nucleotidase signature sequence and evidence strongly indicated that it can convert adenosine monophosphate (AMP) to adenosine. It was designated as Ssads (the adenosine synthase of S. suis 2). Furthermore, we found that Ssads could impair PMN's defense against S. suis 2 with decreasing of oxidative activity and degranulation of PMNs in human blood via A2a receptors. Additionally, this enzyme-deficient mutant was found to have diminished virulence in the piglet infection model. Taken together, these results indicate that Ssads play an important role in S. suis 2 escaping human innate immunity in the context of inhibiting PMN's activity by synthesis of adenosine.

[Anti-phagocytosis mechanism of SalK/SalR, a two-component regulatory system of Streptococcus suis serotype 2].

OBJECTIVE: To determine the role of the two-component regulatory system (TCS) SalK/SalR in the resistance of Streptococcus suis serotype 2 (SS2) phagocytosed by THP-1-derived macrophages (THP-Mphi). METHODS: Using transmission electron microscopy (TEM), the capsular differences between the wild-type strain 05ZYH33 and the mutant δsalKR were observed. The interactions of SS2 with THP-Mphi were monitored by Gram staining and immunofluorescence cytochemistry. The anti-phagocytic activity of SS2 was evaluated by the construction of phagocytosis model of THP-Mphi. RESULTS: The TEM showed that in the mutant δsalKR, the capsule was lost; the Gram staining and immunofluorescence imaging revealed that the absence of salKR caused more SS2 were engulfed by THP-Mphi. The phagocytosis model of THP-Mphi cells further demonstrated that the mutant δsalKR was easier to be phagocytosed by THP-1 cells than the wild-type strain. CONCLUSION: The SalK/SalR regulatory system resists the phagocytosis by THP- Mphi through the capsular formation, but the mechanism of how it regulates the formation of the capsule needs further elucidation.