Gene-Specific Sex Effects on Susceptibility to Infectious Diseases

Inflammation is an integral part of defense against most infectious diseases. These pathogen-induced immune responses are in very many instances strongly influenced by host’s sex. As a consequence, sexual dimorphisms were observed in susceptibility to many infectious diseases. They are pathogen dose-dependent, and their outcomes depend on pathogen and even on its species or subspecies. Sex may differentially affect pathology of various organs and its influence is modified by interaction of host’s hormonal status and genotype: sex chromosomes X and Y, as well as autosomal genes. In this Mini Review we summarize the major influences of sex in human infections and subsequently focus on 22 autosomal genes/loci that modify in a sex-dependent way the response to infectious diseases in mouse models. These genes have been observed to influence susceptibility to viruses, bacteria, parasites, fungi and worms. Some sex-dependent genes/loci affect susceptibility only in females or only in males, affect both sexes, but have stronger effect in one sex; still other genes were shown to affect the disease in both sexes, but with opposite direction of effect in females and males. The understanding of mechanisms of sex-dependent differences in the course of infectious diseases may be relevant for their personalized management.

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Two way relationship of pregnancy and immune responses to infectious diseases

Placenta ◽

10.1016/s0143-4004(96)90101-0 ◽

1996 ◽

Vol 17 (5-6) ◽

pp. A10

Author(s):

L. Krishnan ◽

L.J. Guilbert ◽

T.G. Wegmann ◽

M. Belosevic ◽

T.R. Mosmann

Keyword(s):

Infectious Diseases ◽

Immune Responses ◽

Relationship Of

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Vaccination today and tomorrow

Bioscience Reports ◽

10.1007/bf01204352 ◽

1995 ◽

Vol 15 (6) ◽

pp. 493-502 ◽

Cited By ~ 4

Author(s):

F. Brown

Keyword(s):

Immune Response ◽

Infectious Diseases ◽

Immune Responses ◽

Molecular Level ◽

Critical Issue ◽

Natural Host ◽

Increasing Knowledge ◽

Empirical Approaches

The vaccines against infectious diseases in use today are, with few exceptions, prepared from the causal agents themselves, either by inactivating them with a chemical such as formaldehyde or by attenuating them so that they grow and thus evoke an immune response in the natural host but cause no disease. These empirical approaches have produced many highly successful vaccines. Increasing knowledge at the molecular level of the agents and of the immune response to protein antigent is now providing us with the opportunity to design vaccines that will elicit protective responses without the need to use the agents themselves. The critical issue is to identify the immune responses that correlate with protection.

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Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

Journal of Dairy Research ◽

10.1017/s0022029900031757 ◽

1996 ◽

Vol 63 (2) ◽

pp. 257-267 ◽

Cited By ~ 12

Author(s):

Chun W. Wong ◽

Geoffrey O. Regester ◽

Geoffrey L. Francis ◽

Dennis L. Watson

Keyword(s):

Immune Responses ◽

Bovine Milk ◽

Inhibitory Effect ◽

Dependent Manner ◽

Milk Whey ◽

Significant Difference ◽

Lymphocyte Phenotypes ◽

Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

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Mouse models for infectious diseases caused by Staphylococcus aureus

Journal of Immunological Methods ◽

10.1016/j.jim.2014.04.007 ◽

2014 ◽

Vol 410 ◽

pp. 88-99 ◽

Cited By ~ 68

Author(s):

Hwan Keun Kim ◽

Dominique Missiakas ◽

Olaf Schneewind

Keyword(s):

Staphylococcus Aureus ◽

Infectious Diseases ◽

Mouse Models

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CRISPR-Cas Biology and Its Application to Infectious Diseases

Journal of Clinical Microbiology ◽

10.1128/jcm.01307-18 ◽

2018 ◽

Vol 57 (4) ◽

Cited By ~ 10

Author(s):

Jeffrey R. Strich ◽

Daniel S. Chertow

Keyword(s):

Infectious Diseases ◽

Adaptive Immune System ◽

Biomedical Science ◽

Adaptive Immune ◽

Disease Outcomes ◽

Excess Morbidity ◽

Efficient Gene ◽

Global Threat ◽

Human Infections ◽

Cas Proteins

ABSTRACT Infectious diseases remain a global threat contributing to excess morbidity and death annually, with the persistent potential for destabilizing pandemics. Improved understanding of the pathogenesis of bacteria, viruses, fungi, and parasites, along with rapid diagnosis and treatment of human infections, is essential for improving infectious disease outcomes worldwide. Genomic loci in bacteria and archaea, termed clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, function as an adaptive immune system for prokaryotes, protecting them against foreign invaders. CRISPR-Cas9 technology is now routinely applied for efficient gene editing, contributing to advances in biomedical science. In the past decade, improved understanding of other diverse CRISPR-Cas systems has expanded CRISPR applications, including in the field of infectious diseases. In this review, we summarize the biology of CRISPR-Cas systems and discuss existing and emerging applications to evaluate mechanisms of host-pathogen interactions, to develop accurate and portable diagnostic tests, and to advance the prevention and treatment of infectious diseases.

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Humanized Mouse Models to Study Cell-Mediated Immune Responses to Liver-Stage Malaria Vaccines

Trends in Parasitology ◽

10.1016/j.pt.2015.06.008 ◽

2015 ◽

Vol 31 (11) ◽

pp. 583-594 ◽

Cited By ~ 15

Author(s):

Michael F. Good ◽

Michael T. Hawkes ◽

Stephanie K. Yanow

Keyword(s):

Immune Responses ◽

Mouse Models ◽

Humanized Mouse ◽

Liver Stage ◽

Malaria Vaccines ◽

Humanized Mouse Models

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Pulmonary infection interrupts acute cutaneous wound healing through disruption of chemokine signals

10.1101/2020.05.08.084442 ◽

2020 ◽

Author(s):

Meredith J. Crane ◽

Yun Xu ◽

Sean F. Monaghan ◽

Benjamin M. Hall ◽

Jorge E. Albina ◽

...

Keyword(s):

Wound Healing ◽

Immune Responses ◽

Mouse Models ◽

Pulmonary Infection ◽

Lung Infection ◽

Innate Immune ◽

List Type ◽

Cutaneous Wound Healing ◽

Wound Site ◽

Cutaneous Wound

SummaryStudies of the immune response typically focus on single-insult systems, with little known about how multi-insult encounters are managed. Pneumonia in patients recovering from surgery is a clinical situation that exemplifies the need for the patient to mount two distinct immune responses. Examining this, we have determined that poor wound healing is an unreported complication of pneumonia in laparotomy patients. Using mouse models, we found that lung infection suppressed the trafficking of innate leukocytes to wounded skin, while pulmonary resistance to the bacterial infection was maintained. The dual insults caused distinct systemic and local changes to the inflammatory response, the most striking being a rapid and sustained decrease in chemokine levels at the wound site of mice with pneumonia. Remarkably, replenishing wound chemokine levels completely rescued the wound-healing rate in mice with a pulmonary infection. These findings have broad implications for understanding the mechanisms guiding the innate immune system to prioritize inflammatory sites.One Sentence SummaryChemokine-mediated signaling drives the prioritization of innate immune responses to bacterial pulmonary infection over cutaneous wound healing.HighlightsHuman laparotomy patients with pneumonia have an increased rate of incision dehiscence, and this observation can be recapitulated in mouse models of bacterial lung infections and skin wounds.Lung infection causes rapid and sustained suppression of skin wound chemokine and inflammatory cytokine production as well as leukocyte recruitment.Unique systemic shifts in the immune compartment occur with two inflammatory insults, including the cytokine/chemokine signature and the mobilization, recruitment, and phenotype of innate leukocytes.Restoration of chemokine signaling in the wounds of mice that have a lung infection results in increased neutrophil trafficking to the wound site and rescues the rate of healing.Graphical Abstract

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Altered endochondral ossification in collagen X mouse models leads to impaired immune responses

Developmental Dynamics ◽

10.1002/dvdy.21594 ◽

2008 ◽

Vol 237 (10) ◽

pp. 2693-2704 ◽

Cited By ~ 12

Author(s):

E. Sweeney ◽

M. Campbell ◽

K. Watkins ◽

C.A. Hunter ◽

O. Jacenko

Keyword(s):

Immune Responses ◽

Mouse Models ◽

Endochondral Ossification

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Sex-Dependent Differences in Plasma Cytokine Responses to Hantavirus Infection

Clinical and Vaccine Immunology ◽

10.1128/cvi.00035-08 ◽

2008 ◽

Vol 15 (5) ◽

pp. 885-887 ◽

Cited By ~ 32

Author(s):

Jonas Klingström ◽

Therese Lindgren ◽

Clas Ahlm

Keyword(s):

Sex Differences ◽

Infectious Diseases ◽

Immune Responses ◽

Infectious Agent ◽

Hantavirus Infection ◽

Infected Female ◽

Macrophage Colony Stimulating Factor ◽

Male Patients ◽

Macrophage Colony ◽

Interleukin 9

ABSTRACT There are often sex differences in susceptibility to infectious diseases and in level of mortality after infection. These differences probably stem from sex-related abilities to mount proper or unwanted immune responses against an infectious agent. We report that hantavirus-infected female patients show significantly higher plasma levels of interleukin-9 (IL-9), fibroblast growth factor 2, and granulocyte-macrophage colony-stimulating factor and lower levels of IL-8 and gamma interferon-induced protein 10 than male patients. The results demonstrate that a virus infection can induce sex-dependent differences in acute immune responses in humans. This finding may, at least partly, explain the observed sex differences in susceptibility to infectious diseases and in mortality following infection.

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