Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.
Adult ; Aged ; Aged, 80 and over ; Aging ; genetics ; immunology ; Betacoronavirus ; CD4-Positive T-Lymphocytes ; metabolism ; Cell Lineage ; Chromatin Assembly and Disassembly ; Coronavirus Infections ; immunology ; Cytokine Release Syndrome ; etiology ; immunology ; Cytokines ; biosynthesis ; genetics ; Disease Susceptibility ; Flow Cytometry ; methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Rearrangement ; Humans ; Immune System ; cytology ; growth & development ; immunology ; Immunocompetence ; genetics ; Inflammation ; genetics ; immunology ; Mass Spectrometry ; methods ; Middle Aged ; Pandemics ; Pneumonia, Viral ; immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; Young Adult

Adult ; Aged ; Aqueous Humor ; virology ; Female ; Humans ; Immunocompetence ; immunology ; Inflammation ; virology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

Although chronic obstructive pulmonary disease (COPD) is regarded as a chronic inflammatory lung disease, the disease mechanism is still not known. Intriguingly, aging lungs are quite similar to COPD-affected lungs in many ways, and COPD has been viewed as a disease of accelerated premature aging of the lungs. In this paper, based on a literature review, we would like to propose immunosenescence, age-associated decline in immunity, as a critical mechanism for the development of COPD. Immunosenescence can cause a low-grade, systemic inflammation described as inflammaging. This inflammaging may be directly involved in the COPD pathogenesis. The potential contributors to the development of inflammaging in the lungs possibly leading to COPD are discussed in the review paper. A notable fact about COPD is that only 15% to 20% of smokers develop clinically significant COPD. Given that there is a substantial inter-individual variation in inflammaging susceptibility, which is genetically determined and significantly affected by the history of the individual's exposure to pathogens, immunosenescence and inflammaging may also provide the answer for this unexpectedly low susceptibility of smokers to clinically significant COPD.
Aging ; Aging, Premature ; Immunosenescence ; Inflammation ; Lung ; Lung Diseases ; Pulmonary Disease, Chronic Obstructive

Pyogenic liver abscess (PLA) can be caused by bacteria entering the liver via the portal vein or primary bacteremia, or it can be cryptogenic. Recently, Klebsiella pneumoniae has been increasingly found as a PLA pathogen. PLA due to this bacterium often leads to formation of extrahepatic abscesses. The treatment of choice is dual therapy with insertion of percutaneous catheter drainage and antibiotic therapy. We report 2 cases of PLA due to K. pneumoniae in immunocompetent children. We successfully treated patient 1 with percutaneous catheter drainage for 18 days and 6-week course of antibiotic therapy. Patient 2 was treated with percutaneous needle aspiration and antibiotic therapy for the same period. In both patients, the PLAs showed the ultrasound-confirmed resolutions after the dual therapy.
Abscess ; Anti-Bacterial Agents ; Bacteremia ; Bacteria ; Catheters ; Child ; Drainage ; Humans ; Immunocompetence ; Klebsiella pneumoniae ; Klebsiella ; Liver ; Liver Abscess, Pyogenic ; Needles ; Pneumonia ; Portal Vein

BACKGROUND: The prevalence of acute kidney injury (AKI) in elderly patients has grown considerably. Age-associated changes in the immune system can be one of the critical factors determining AKI outcomes. This study aimed to investigate the role of senescence of bone marrow (BM)-derived cells in the development of AKI, focusing on the immune response. METHODS: Female 7-week-old C57BL/6 mice were irradiated and treated with BM cells from either 48-week-old or 8-week-old male mice. Ischemia-reperfusion injury (IRI) was induced, and their functional deterioration, histological tubular damage, and inflammatory responses were compared. For the in-vitro study, lipopolysaccharide (LPS)-stimulated cytokine production by BM cells from old and young mice were examined. RESULTS: At 24 hours after IRI, there was no significant difference in the number of circulating immune cells between the mice transplanted with old or young BM cells. However, the mice with old BM cells showed less functional deterioration and histological tubular injury than those with young BM cells. Moreover, macrophage infiltration and renal cytokine interleukin (IL)-12 levels were lower in the mice with old BM cells at 24 hours post-IRI. Consistently, the in vitro study showed that LPS-induced production of cytokines interferon-γ, monocyte chemoattractant protein-1, and IL-10 was attenuated in cultured old BM cells, suggesting that age-related functional changes in these cells may lead to reduced inflammation in IRI. CONCLUSION: Immunosenescence could affect the susceptibility and response to renal IRI. Further studies specifically addressing age-related alterations can help in the development of treatment strategies for elderly patients with AKI.
Acute Kidney Injury ; Aged ; Aging ; Animals ; Bone Marrow Cells ; Bone Marrow ; Chemokine CCL2 ; Cytokines ; Female ; Humans ; Immune System ; Immunosenescence ; In Vitro Techniques ; Inflammation ; Interleukin-10 ; Interleukins ; Macrophages ; Male ; Mice ; Prevalence ; Reperfusion Injury

Immunosenescence is characterized by a progressive deterioration of the immune system associated with aging. Multiple components of both innate and adaptive immune systems experience aging-related changes, such as alterations in the number of circulating monocytic and dendritic cells, reduced phagocytic activities of neutrophils, limited diversity in B/T cell repertoire, T cell exhaustion or inflation, and chronic production of inflammatory cytokines known as inflammaging. The elderly are less likely to benefit from vaccinations as preventative measures against infectious diseases due to the inability of the immune system to mount a successful defense. Therefore, aging is thought to decrease the efficacy and effectiveness of vaccines, suggesting aging-associated decline in the immunogenicity induced by vaccination. In this review, we discuss aging-associated changes in the innate and adaptive immunity and the impact of immunosenescence on viral infection and immunity. We further explore recent advances in strategies to enhance the immunogenicity of vaccines in the elderly. Better understanding of the molecular mechanisms underlying immunosenescence-related immune dysfunction will provide a crucial insight into the development of effective elderly-targeted vaccines and immunotherapies.
Adaptive Immunity ; Aged ; Aging ; Communicable Diseases ; Cytokines ; Dendritic Cells ; Humans ; Immune System ; Immunosenescence ; Immunotherapy ; Inflation, Economic ; Neutrophils ; Vaccination ; Vaccines

In many countries, vaccines are used for the prevention of foot-and-mouth disease (FMD). However, because there is no protection against FMD immediately after vaccination, research and development on antiviral agents is being conducted to induce protection until immunological competence is produced. This study tested whether well-known chemicals used as RNA virus treatment agents had inhibitory effects on FMD viruses (FMDVs) and demonstrated that ribavirin showed antiviral effects against FMDV in vitro/in vivo. In addition, it was observed that combining the administration of the antiviral agents orally and complementary therapy with vaccines synergistically enhanced antiviral activity and preserved the survival rate and body weight in the experimental animals. Antiviral agents mixed with an adjuvant were inoculated intramuscularly along with the vaccines, thereby inhibiting virus replication after injection and verifying that it was possible to induce early protection against viral infection prior to immunity being achieved through the vaccine. Finally, pigs treated with antiviral agents and vaccines showed no clinical signs and had low virus excretion. Based on these results, it is expected that this combined approach could be a therapeutic and preventive treatment for early protection against FMD.
Animals ; Antiviral Agents ; Body Weight ; Foot-and-Mouth Disease ; Immunocompetence ; Ribavirin ; RNA Viruses ; Survival Rate ; Swine ; Vaccination ; Vaccines ; Virus Replication

Disseminated herpes zoster commonly occurs in patients with decreased immunity, but rarely in patients without any evidence of immunosuppression. We reported a case of disseminated herpes zoster with visceral organ involvement in a non-immunocompromised patient. An 83-year-old man visited our pain center, with chief complaints of painful rashes on the L3–L4 and S2–S4 due to acute herpes zoster. Even though intravenous antiviral therapy was initiated immediately upon hospitalization, his lesion deteriorated and systemic cluster formed. Urinary retention and hyponatremia occurred, and he was diagnosed with zoster cystitis and severe inappropriate antidiuretic hormone syndrome. Conservative treatment, including Foley catheter insertion and correction of hyponatremia with antiviral therapy, was initiated, and he was discharged without any complications at the 33rd day of hospitalization. Old age can be a risk factor of disseminated herpes zoster, and visceral organ involvement should also be considered.
Aged ; Aged, 80 and over ; Catheters ; Cystitis ; Exanthema ; Herpes Zoster ; Hospitalization ; Humans ; Hyponatremia ; Immunocompetence ; Immunosuppression ; Inappropriate ADH Syndrome ; Pain Clinics ; Risk Factors ; Urinary Bladder ; Urinary Retention

OBJECTIVE: To investigate the etiological and clinical characteristics of immunocompetent patients with candidemia. METHODS: The clinical and microbiological data of patients diagnosed as candidemia admitted in Peking University Third Hospital from January 2010 to June 2016 were retrospectively analyzed. Underlying diseases, Candida spp. colonization, clinical manifestations, microbiological data, treatment and the outcome were compared between the HIV-negative immunocompromised (IC) and nonimmunocompromised (NIC) patients. RESULTS: A total of 62 cases diagnosed as candidemia were analyzed including 36 men and 26 women, with 16 to 100 years of age [(66.02±17.65) years]. There were 30 NIC and 32 HIV-negative IC patients respectively. In the NIC patients, there were 19 cases (19/30, 63.33%) with admission in intensive care unit (ICU), 21 (21/30, 70.00%) associated diabetes mellitus or uncontrolled hyperglycemia and 22 (22/30,73.33%) receiving invasive mechanical ventilation, while in the HIV-negative IC patients, there were 8 (8/32, 25.00%), 13 (13/32, 40.63%) and 7 (7/32, 21.88%) respectively (P<0.05). The NIC patients had higher acute physiology and chronic health evaluation (APACHE II) scores and sequential organ failure assessment (SOFA) scores both at admission (19.98±5.81, 6.04±6.14) and candidemia onset (25.61±6.52, 12.75±8.42) than the HIV-negative IC patients (APACHEII 15.09±5.82, 22.15±5.98) and SOFA 2.87±2.73, 7.66±5.64 respectively (P<0.05). In the NIC patients, twenty-one cases (21/30, 70.00%) died in hospital, while 14 cases (14/32, 43.75%) in HIV-negative IC. The crude mortality was significantly different between the two groups (P<0.05). By blood culture, Canidia albicans remained the the most prevalent isolates in all the patients. Clinical manifestation, Candida spp. colonization, etiology and drug susceptibility were also similar between NIC and HIV-negative IC patients (P>0.05). CONCLUSION Candidemia in NIC patients tends to occur in those who are much more critically ill, more often admitted in ICU, and more frequently have diabetes mellitus or uncontrolled hyperglycemia and receive invasive mechanical ventilation than HIV-negative IC patients. NIC patients also have poorer prognosis than HIV-negative IC patients. Clinical manifestations, and microbiological characteristics are similar between HIV-negative IC and NIC patients.
APACHE ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Candida ; Candidemia/therapy* ; Candidiasis/therapy* ; Female ; Humans ; Immunocompetence ; Intensive Care Units ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Young Adult

Septic arthritis of acromioclavicular (AC) joint is a rare entity. It is generally seen in patients who are immunocompromised. Only 15 cases have been reported till now, with only one case series of 6 patients. We report a case of septic arthritis of AC joint in an immunocompetent child. A 9 years old girl presented with history of pain in left shoulder for 4 days associated with fever. No history suggestive of any immunocompromised state was complained. On local examination, a swelling of around 3 cm in diameter was found over left AC joint region with raised local temperature, tenderness on palpation and positive response in fluctuation test. Total leukocyte count was 18.7 × 10/L with 80% of neutrophils. Erythrocyte sedimentation rate (ESR) was 28 mm/1 h. C-reactive protein (CRP) was 12 mg/L. X-ray showed enlarged left AC joint space. Ultrasound revealed hypoechoic collection in the AC joint and the surrounding area. The aspirate was thick and purulent in nature, revealing Gram positive cocci at staining. Arthrotomy and thorough lavage of AC joint was done. Culture of the aspirate showed Methicillin Resistant Staphylococcus Aureus (MRSA) after 48 hours that was sensitive to amikacin, gentamicin, erythromycin and teicoplanin. Patient was symptom-free at 2 months of follow-up with no signs of osteomyelitis on the radiographs. Thus this is the first case of AC joint septic arthritis in healthy individual. Being proximal to the shoulder joint, AC joint septic arthritis can be confused with the shoulder joint septic arthritis. Thus, high index of suspicion is required for accurate diagnosis.
Acromioclavicular Joint ; Anti-Bacterial Agents ; therapeutic use ; Arthritis, Infectious ; diagnosis ; therapy ; Child ; Female ; Humans ; Immunocompetence