A natural substitution of a conserved amino acid in eIF4E confers resistance against multiple potyviruses.

Eukaryotic translation initiation factor 4E (eIF4E), which plays a pivotal role in initiating translation in eukaryotic organisms, is often hijacked by the viral genome-linked protein to facilitate the infection of potyviruses. In this study, we found that the naturally occurring amino acid substitution D71G in eIF4E is widely present in potyvirus-resistant watermelon accessions and disrupts the interaction between watermelon eIF4E and viral genome-linked protein of papaya ringspot virus-watermelon strain, zucchini yellow mosaic virus or watermelon mosaic virus. Multiple sequence alignment and protein modelling showed that the amino acid residue D71 located in the cap-binding pocket of eIF4E is strictly conserved in many plant species. The mutation D71G in watermelon eIF4E conferred resistance against papaya ringspot virus-watermelon strain and zucchini yellow mosaic virus, and the equivalent mutation D55G in tobacco eIF4E conferred resistance to potato virus Y. Therefore, our finding provides a potential precise target for breeding plants resistant to multiple potyviruses.

Novel biotin-linked amphiphilic calix[4]arene-based supramolecular micelles as doxorubicin carriers for boosted anticancer activity.

Supramolecular carrier-mediated chemotherapy is a highly attractive strategy for targeted drug delivery. In this study, four novel biotin-linked calix[4]arenes BPCA1-BPCA4 have been rationally designed to construct nano-complex with doxorubicin. The in vitro and in vivo assessments reveal that BPCA4-DOX with excellent stability are capable of affording significantly superior anti-tumor activity and lower side effects.

Effects of linalool on Botrytis cinerea growth and control of tomato gray mold.

We examined the antifungal characteristics of linalool against Botrytis cinerea using plate inhibition assay and spore germination assay, and assessed the capacity of linalool in controlling tomato gray mold disease via tomato pot inoculation assay. The results showed that linalool exhibited strong inhibitive effects on mycelial growth of B. cinerea, with an EC50 value of 0.581 mL·L-1. In the spore germination test, linalool treatment inhibited spore germination in a dose-dependent manner. The electric conductivity and the malondialdehyde (MDA) contents were significantly increased in linalool-treated B. cinerea than that of the control, indicating that linalool induced oxidative damage and destroyed the cell membrane integrity in B. cinerea. The activities of the superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in the linalool-treated B. cinerea were decreased significantly by 27.4%, 68.9% and 26.0%, respectively, suggesting that linalool inhibited the antioxidant activity of B. cinerea. In the pot experiment, the diameter of lesions in linalool-treated tomatoes was significantly smaller than that of the control. The activities of SOD, POD, CAT, polyphenol oxidase, and phenylalnine ammonialyase in the linalool-treated tomatoes increased, while the MDA content decreased, suggesting that linalool could alleviate the oxidative damage caused by B. cinerea and promote plant disease resistance. In summary, linalool had inhibitory effect on the growth of B. cinerea and could control gray mold disease in tomatoes. These findings could lay the foundation for developing bota-nical antifungal agents for management of tomato gray mold disease.

A novel homozygous frameshift variant in DNAH8 causes multiple morphological abnormalities of the sperm flagella in a consanguineous Pakistani family.

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate. Whole-exome sequencing (WES) is used to detect pathogenic variants in patients with MMAF. In this study, a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8) from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Furthermore, an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa. Collectively, our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.

A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms.

Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.

CFTR mutations causing congenital unilateral absence of the vas deferens (CUAVD) and congenital absence of the uterus (CAU) in a consanguineous family.

Cystic fibrosis (CF) is one of the most common recessive genetic diseases, with a wide spectrum of phenotypes, ranging from infertility to severe pulmonary disease. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are considered the main genetic cause for CF. In this study, we recruited a consanguineous Iranian pedigree with four male patients diagnosed with congenital unilateral absence of the vas deferens (CUAVD), and one female patient diagnosed with congenital absence of the uterus (CAU). Testicular biopsy of one patient was performed, and hematoxylin and eosin (H and E) staining of testis sections displayed the presence of germ cell types ranging from spermatogonia to mature spermatids, indicating obstructive azoospermia. To explore the underlying genetic factor in this familial disorder, we therefore performed whole-exome sequencing (WES) on all available family members. WES data filtration and CFTR haplotype analysis identified compound heterozygous mutations in CFTR among four patients (two CUAVD patients carried p.H949Y and p.L997F, and one CUAVD and the female CAU patient carried p.H949Y and p.I148T). All these mutations were predicted to be deleterious by at least half of the prediction software programs and were confirmed by Sanger sequencing. Our study reported that CFTR compound heterozygous mutations in a consanguineous Iranian family cause infertility in both sexes.

Genome sequencing identified novel mechanisms underlying virescent mutation in upland cotton Gossypiuma hirsutum.

BACKGROUND: Virescent mutation broadly exists in plants and is an ideal experimental material to investigate regulatory mechanisms underlying chlorophyll synthesis, photosynthesis and plant growth. Up to date, the molecular mechanisms in two virescent mutations have been clarified in cottons (Gossypiuma hirsutum). A virescent mutation has been found in the cotton strain Sumian 22, and the underlying molecular mechanisms have been studied. METHODS: The virescent mutant and wild type (WT) of Sumian 22 were cross-bred, and the F1 population were self-pollinated to calculate the segregation ratio. Green and yellow leaves from F2 populations were subjected to genome sequencing and bulked-segregant analysis was performed to screen mutations. Real-time quantitative PCR (RT-qPCR) were performed to identify genes in relations to chlorophyll synthesis. Intermediate products for chlorophyll synthesis were determined to validate the RT-qPCR results. RESULTS: The segregation ratio of green and virescent plants in F2 population complied with 3:1. Compared with WT, a 0.34 Mb highly mutated interval was identified on the chromosome D10 in mutant, which contained 31 genes. Among them, only ABCI1 displayed significantly lower levels in mutant than in WT. Meanwhile, the contents of Mg-protoporphyrin IX, protochlorophyllide, chlorophyll a and b were all significantly lower in mutant than in WT, which were consistent with the inhibited levels of ABCI1. In addition, a mutation from A to T at the -317 bp position from the start codon of ABCI1 was observed in the genome sequence of mutant. CONCLUSIONS: Inhibited transcription of ABCI1 might be the mechanism causing virescent mutation in Sumian 22 cotton, which reduced the transportation of protoporphyrin IX to plastid, and then inhibited Mg-protoporphyrin IX, Protochlorophyllide and finally chlorophyll synthesis. These results provided novel insights into the molecular mechanisms underlying virescent mutation in cotton.

Novel biallelic loss-of-function mutations in CFAP43 cause multiple morphological abnormalities of the sperm flagellum in Pakistani families.

Multiple morphological abnormalities of the sperm flagella (MMAF) is a specific type of asthenoteratozoospermia, presenting with multiple morphological anomalies in spermatozoa, such as absent, bent, coiled, short, or irregular caliber flagella. Previous genetic studies revealed pathogenic mutations in genes encoding cilia and flagella-associated proteins (CFAPs; e.g., CFAP43, CFAP44, CFAP65, CFAP69, CFAP70, and CFAP251) responsible for the MMAF phenotype in infertile men from different ethnic groups. However, none of them have been identified in infertile Pakistani males with MMAF. In the current study, two Pakistani families with MMAF patients were recruited. Whole-exome sequencing (WES) of patients and their parents was performed. WES analysis reflected novel biallelic loss-of-function mutations in CFAP43 in both families (Family 1: ENST00000357060.3, p.Arg300Lysfs*22 and p.Thr526Serfs*43 in a compound heterozygous state; Family 2: ENST00000357060.3, p.Thr526Serfs*43 in a homozygous state). Sanger sequencing further confirmed that these mutations were segregated recessively in the families with the MMAF phenotype. Semiquantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) was carried out to detect the effect of the mutation on mRNA of the affected gene. Previous research demonstrated that biallelic loss-of-function mutations in CFAP43 accounted for the majority of all CFAP43-mutant MMAF patients. To the best of our knowledge, this is the first study to report CFAP43 biallelic loss-of-function mutations in a Pakistani population with the MMAF phenotype. This study will help researchers and clinicians to understand the genetic etiology of MMAF better.

The CNOT4 Subunit of the CCR4-NOT Complex is Involved in mRNA Degradation, Efficient DNA Damage Repair, and XY Chromosome Crossover during Male Germ Cell Meiosis.

The CCR4-NOT complex is a major mRNA deadenylase in eukaryotes, comprising the catalytic subunits CNOT6/6L and CNOT7/8, as well as CNOT4, a regulatory subunit with previously undetermined functions. These subunits have been hypothesized to play synergistic biochemical functions during development. Cnot7 knockout male mice have been reported to be infertile. In this study, viable Cnot6/6l double knockout mice are constructed, and the males are fertile. These results indicate that CNOT7 has CNOT6/6L-independent functions in vivo. It is also demonstrated that CNOT4 is required for post-implantation embryo development and meiosis progression during spermatogenesis. Conditional knockout of Cnot4 in male germ cells leads to defective DNA damage repair and homologous crossover between X and Y chromosomes. CNOT4 functions as a previously unrecognized mRNA adaptor of CCR4-NOT by targeting mRNAs to CNOT7 for deadenylation of poly(A) tails, thereby mediating the degradation of a subset of transcripts from the zygotene to pachytene stage. The mRNA removal promoted by the CNOT4-regulated CCR4-NOT complex during the zygotene-to-pachytene transition is crucial for the appropriate expression of genes involved in the subsequent events of spermatogenesis, normal DNA double-strand break repair during meiosis, efficient crossover between X and Y chromosomes, and ultimately, male fertility.

Semen parameters in men recovered from COVID-19.

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.

Effects of vermicompost fertilization on soil, tomato yield and quality in greenhouse.

The excessive use of chemical fertilizer on vegetables in protected facilities resulted in soil degradation, serious soil-borne diseases, and lower vegetable yield and quality. We examined the effects of vermicompost on soil nutrient, enzyme activities, microbial quantity, tomato growth, yield and quality in greenhouse. The results showed that both broadcast and furrow application of vermicompost improved soil environment, and significantly increased contents of soil organic matter and soil nutrients (nitrogen, phosphorus and potassium). Vermicompost application significantly increased sucrase and catalase activities, abundance of bacteria and actinomycetes, and decreased the abundance of fungi in the soil. Furrow application but not the broadcast application promoted the growth of tomato plants. The vermicompost promoted root activities and leaf photosynthesis, increased chlorophyll, nitrogen and potassium contents in leaves. Broadcast and furrow application of vermicompost significantly increased tomato yield by 22.7% and 32.6%, respectively. Furrow application increased the contents of soluble protein, soluble sugar, vitamin C and titratable acid by 66.1%, 11.0%, 122.6% and 29.9%, respectively, and decreased nitrate content in tomato fruits by 65.7%. However, broadcast application did not affect fruit quality.

The molecular control of meiotic double-strand break (DSB) formation and its significance in human infertility.

Meiosis is an essential step in gametogenesis which is the key process in sexually reproducing organisms as meiotic aberrations may result in infertility. In meiosis, programmed DNA double-strand break (DSB) formation is one of the fundamental processes that are essential for maintaining homolog interactions and correcting segregation of chromosomes. Although the number and distribution of meiotic DSBs are tightly regulated, still abnormalities in DSB formation are known to cause meiotic arrest and infertility. This review is a detailed account of molecular bases of meiotic DSB formation, its evolutionary conservation, and variations in different species. We further reviewed the mutations of DSB formation genes in association with human infertility and also proposed the future directions and strategies about the study of meiotic DSB formation.

Effects of biochar and dicyandiamide combination on nitrous oxide emissions from Camellia oleifera field soil.

Greenhouse gas emissions from agricultural soils contribute substantially to global atmospheric composition. Nitrous oxide (N2O) is one important greenhouse gas induces global warming. Nitrification inhibitors (NI) or biochar can be effective soil N2O emission mitigation strategies for agricultural soils. However, due to differences in crop physiological traits or agricultural management, the effectiveness of mitigation strategies varies among agricultural systems. Camellia oleifera is a woody oil plant widely grown and requires intensive N input, which will potentially increase N2O emissions. Thereby, mitigation of N2O emissions from C. oleifera field soil is vital for sustainable C. oleifera development. Besides NI, incorporation of C. oleifera fruit shell-derived biochar into its soil will benefit waste management and simultaneous mitigation of N2O emissions but this has not been investigated. Here, we conducted two studies to examine effects of biochar addition and NI (dicyandiamide, DCD) application on N2O emissions from C. oleifera field soil with different N (urea or NH4NO3) and incubation temperatures. Biochar effects on nitrification rates varied among N treatments. Biochar applied in combination with DCD further reduced nitrification rates (for urea treatment, decreased from 1.1 to 0.3 mg kg-1 day-1). Biochar addition consistently increased soil N2O emissions (for urea treatment, increased from 0.03 to 0.08 ng g-1 h-1) and their temperature sensitivity. DCD application reduced soil N2O emissions with greater reductions with urea application. In future cultivation of intensively managed C. oleifera gardens, NI should be applied to mitigate N2O emissions if biochar is added, especially when urea is used.

[Optimizing fertilization scheme of N, P2O5 and K2O concentration for eggplant under soilless culture.] / èŒ„å­æ— åœŸæ ½åŸ¹æ°®ç£·é’¾æµ“åº¦ä¼˜åŒ–æ–½è‚¥æ–¹æ¡ˆ.

To get optimal nitrogen (N), phosphorus (P2O5) and potassium (K2O) concentrations range for high quality and yield of eggplant with vermiculite as cultivation substrate, three factors and quadratic saturation D-optimal regression (310) were used to establish a ternary quadratic mathematical model with N, P2O5 and K2O concentrations as independent variables and eggplant yield and quality as objective functions. The results showed that yield and quality of eggplants were significantly influenced by N, P2O5 and K2O concentrations. The yield was most influenced by K2O concentration, and followed by N and then P2O5. The quality was also most influenced by K2O concentration, and followed by P2O5 and then N. There were significant interactive effects of N+P2O5, N+K2O and P2O5+K2O on yield, and significant interaction of N+K2O on eggplant quality. Under lower concentrations, the yield and quality of eggplants enhanced with the increasing N, P2O5 and K2O concentrations. When the nutrient concentrations exceeded a threshold, both yield and quality decreased. According to computer simulations, the yield could reach to 3600 g·plant-1 when the fertilization schemes were N 16.0-20.0 mmol·L-1, P2O5 2.2-2.6 mmol·L-1 and K2O 9.9-12.9 mmol·L-1; the fertilization scheme needed to obtain a comprehensive quality score of higher than 90 were N 18.0-21.1 mmol·L-1, P2O5 1.9-2.6 mmol·L-1 and K2O 10.6-13.3 mmol·L-1. In summary, fertilization scheme of high yield (43.2 kg·plot-1) and high quality(comprehensive score of higher than 90) of eggplants were N 18.0-20.0 mmol·L-1, P2O5 2.2-2.6 mmol·L-1, K2O 10.6-12.9 mmol·L-1, with an appropriate N, P2O5 and K2O proportion of 1:0.13:0.62.

[Effects of exogenous 2,4-epibrassinolide on the growth and redox balance of cucumber seedlings under NaHCO3 stress]. / å¤–æºè¡¨æ²¹èœç´ å† é ¯å¯¹NaHCO3胁迫下黄瓜幼苗生长及氧化还原平衡的影响.

The effects of 0.2 µmol·L-1 exogenous 2,4-epibrassinolide (EBR) on the growth and reactive oxygen species metabolism of cucumber seedlings ('Jinyan 4' cucumber) under salt-alkaline stress (30 mmol·L-1 NaHCO3) were examined by hydroponics method. The results showed that NaHCO3 stress significantly induced production of O2-· and accumulation of H2O2 in leaves and roots, resulting in the increases of MDA content and electrolyte leakage. Under NaHCO3 stress, activities of superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, dehydroascorbatereductase, monodehydrodroascorbate reductase, and glutathione reductase as well as contents of ascorbic acid and glutathione were firstly increased and then decreased with progress of stress time. Exogenous EBR application significantly increased the activities of antioxidant enzymes and contents of antioxidants as well as the ratio of AsA/DHA (dehydroascorbic acid) and GSH/GSSG (L-glutathione oxidized) in leaves and roots of cucumber under NaHCO3 stress. Such changes improved the redox hemostasis in plants, reduced the level of reactive oxygen species, and alleviated the membrane lipid peroxidation. Together, they increased the alkaline tolerance of cucumber seedlings.

Modulation of liver regeneration via myeloid PTEN deficiency.

Molecular mechanisms that modulate liver regeneration are of critical importance for a number of hepatic disorders. Kupffer cells and natural killer (NK) cells are two cell subsets indispensable for liver regeneration. We have focused on these two populations and, in particular, the interplay between them. Importantly, we demonstrate that deletion of the myeloid phosphatase and tensin homolog on chromosome 10 (PTEN) leading to an M2-like polarization of Kupffer cells, which results in decreased activation of NK cells. In addition, PTEN-deficient Kupffer cells secrete additional factors that facilitate the proliferation of hepatocytes. In conclusion, PTEN is critical for inhibiting M2-like polarization of Kupffer cells after partial hepatectomy, resulting in NK cell activation and thus the inhibition of liver regeneration. Furthermore, PTEN reduces growth factor secretion by Kupffer cells. Our results suggest that targeting PTEN on Kupffer cells may be useful in altering liver regeneration in patients undergoing liver resection.

[Effects of iron deficiency and NO3- stress on tomato seedlings growth and iron absorption under suboptimal temperature]. / äºšé€‚æ¸©æ¡ä»¶ä¸‹ç¼ºé“å’Œç¡é ¸ç›èƒè¿«å¯¹ç•ªèŒ„å¹¼è‹—ç”Ÿé•¿åŠé“å¸æ”¶çš„å½±å“.

The effects of iron deficiency and NO3- stress on the growth and the iron absorption cha-racteristic of tomato seedlings were investigated under suboptimal temperature (18 ℃/12 ℃ (day/night)). The results indicated that the growth was significantly inhibited under suboptimal temperature compared with appropriate temperature treatment; the plant heights, leaf areas and dry matter accumulations were markedly decreased. The effects of iron deficiency under suboptimal temperature on the growth of tomato seedlings were larger than that of under appropriate temperature treatments. Under suboptimal temperature, the plant heights of tomato seedlings in iron deficiency and/or NO3- stress treatments were not significantly different from no stress treatment, but leaf areas and leaf chlorophyll content of tomato seedlings were decreased obviously. The leaf electrolytic leakage, root activity and Fe3+ reductase activity of tomato seedlings were markedly increased under suboptimal temperature, but chlorophyll content, total root length, root surface area, root tip number and root volume were obviously reduced. The iron contents in roots, stems and leaves of tomato seedlings were also remarkably decreased. The NO3- stress and the combined stress of iron deficiency and NO3- stress under suboptimal temperature aggravated the reduction of dry matter, leaf electrolytic leakage and the inhibition of iron ion absorption in tomato seedlings. The iron ion absorption showed the antagonistic impact on the absorption of potassium and calcium ion, but showed different effects among different organs. The iron deficiency symptom of tomato seedlings was aggravated by reducing the concentration of iron ion in the nutrient solution.

[Effects of sodium nitroprusside on growth and physiological characteristics of tomato seedlings under iron deficiency and NO3- stress]. / ç¡æ™®é’ å¯¹ç¼ºé“å’Œç¡é ¸ç›èƒè¿«ä¸‹ç•ªèŒ„å¹¼è‹—ç”Ÿé•¿åŠç”Ÿç†ç‰¹æ€§çš„å½±å“.

The solution culture method was used to study the effects of sodium nitroprusside (SNP) on plant growth, nutrient uptake and antioxidant enzyme activities of tomato seedlings under iron deficiency and NO3- stress. The results indicated that after 7 d of treatment, iron deficiency inhibited the tomato seedling growth, decreased chlorophyll (a and b) and carotenoid contents, and led to obvious chlorosis; iron deficiency also reduced the activity of SOD, POD and CAT, resulting in significant accumulation of MDA contents and higher electrolytic leakage; proline and soluble sugar contents were not significantly changed; contents of N, P, K, Ca, Mg and Fe in both leaves and roots of tomato seedlings were decreased under iron deficiency in varying degrees. The combined stress of NO3- stress and iron deficiency promoted the inhibition of plant growth, decreased chlorophyll (a and b), carotenoid contents and the activities of SOD, POD and CAT; electrolytic leakage MDA, proline and soluble sugar contents of N, P, Mg, Fe in both leaves and roots of tomato seedlings were much lower, but the contents of K and Ca were significantly increased. Compared to the treatment without SNP, adding 0.1 mmol·L-1 SNP could alleviate the growth inhibition of stressed tomato seedlings. Adding 0.1 mmol·L-1 SF (sodium ferrocyanide) also showed alleviating or promoting effect on some above indexes including the activity of SOD, POD and CAT to some degree, but the other physiological indexes were not significantly changed because iron was contained in SF.

Forkhead Box O1 Regulates Macrophage Polarization Following Staphylococcus aureus Infection: Experimental Murine Data and Review of the Literature.

The functions of macrophages that lead to effective host responses are critical for protection against Staphylococcus aureus. Deep tissue-invading S. aureus initially countered by macrophages trigger macrophage accumulation and induce inflammatory responses through surface receptors, especially toll-like receptor 2 (TLR2). Here, we found that macrophages formed sporadic aggregates in the liver during infection. Within those aggregates, macrophages co-localized with T cells and were indispensable for their infiltration. In addition, we have focused on the mechanisms underlying the polarization of macrophages in Forkhead box transcription factor O1 (FoxO1) conditional knockout Lys Cre/+ FoxO1 fl/fl mice following S. aureus infection and report herein that macrophage M1-M2 polarization via TLR2 is intrinsically regulated by FoxO1. Indeed, for effective FoxO1 activity, stimulation of TLR2 is essential. However, following S. aureus challenge, there was a decrease in macrophage FoxO1, with increased phosphorylation of FoxO1 because of TLR2-mediated activation of PI3K/Akt and c-Raf/MEK/ERK pathway. Following infection in Lys Cre/+ FoxO1 fl/fl mice, mice became more susceptible to S. aureus with reduced macrophage aggregation in the liver and attenuated Th1 and Th17 responses. FoxO1 abrogation reduced M1 pro-inflammatory responses triggered by S. aureus and enhanced M2 polarization in macrophages. In contrast, overexpression of FoxO1 in macrophages increased pro-inflammatory mediators and functional surface molecule expression. In conclusion, macrophage FoxO1 is critical to promote M1 polarization and maintain a competent T cell immune response against S. aureus infection in the liver. FoxO1 regulates macrophage M1-M2 polarization downstream of TLR2 dynamically through phosphorylation.