Immune Response in Bacterial and Candida Sepsis

Abstract

Sepsis leads to a systemic immune response, and despite the progress of modern medicine, it is still responsible for a high mortality rate. The immune response to sepsis is dependent on the innate and adaptive immune systems. The first line is the innate system, which requires complex and multiple pathways in order to eliminate the invading threats. The adaptive responses start after the innate response. The cell-mediated arm of CD4+ and CD8+ T and B cells is the main responsible for this response. A coordinated cytokine response is essential for the host immune response. A dysregulated response can lead to a hyperinflammatory condition (cytokine storm). This hyperinflammation leads to neutrophils activation and may also lead to organ dysfunction. An imbalance of this response can increase the anti-inflammatory response, leading to compensatory anti-inflammatory response syndrome (CARS), persistent inflammation-immunsupression, catabolism syndrome (PICS), and, above all, an immune paralysis stat. This immune paralysis leads to opportunistic infections, Candida species being one of the emerging microorganisms involved. The host immune response is different for bacterial or Candida sepsis. Immune responses for bacterial and Candida sepsis are described in this paper.

Keywords: CARS; Candida sepsis; ICU; PICS; cytokine storm; host immune response; immune paralysis; immune response; sepsis.

Figure 1.

Differentiation of Th naïve cells. There are 4 subtypes of T-helper cells. For each Th activation, an induction of different immunities and associated cytokines of production is released

Figure 2.

Differentiation of B naïve cells. In adaptive immune responses, activation of effector B cells induce the response of different Th response and cytokines

Figure 3.

Recognition of Candida species is mediated by Toll-like receptors (TLRs), C-type lectin receptors (CLRs) and nucleotide-binding oligomerization domain (NOD) receptors. Both TLR4/TLR2 can induce production of proinflammatory signals and cytokines through the MyD88-dependent NF-κ B pathway. However, TLR3-mediated recognition is carried out through activation of the IRF3 transcription factor. The CLR receptors, such as dectin-1, dectin-2, dectin-3, and Mincle, stimulate the release of inflammatory cytokines by activating T cell lineage-specific tyrosine kinase (Syk) and downstream complex (CARD9-Bcl10-MALT1). Dectin-1 promotes maturation of inflammasome, so as to induce production of cytokines. DC-specific intracellular adhesion molecule-grabbing non-integrin (DC-SIGN) receptor can induce T_H cell responses through Raf1 activation. In addition, NLRP3 stimulates reactive oxygen species (ROS) production through an Erk dependent pathway, and NOD2 receptor activates inflammasome by affecting maturation of IL-1β via caspase-1

Figure 4.

After sepsis, an hyperacute phase of hyperinflammation starts. At the same time, an immunosuppression response begins. Following this response, critically ill patients can return to homeostasis and have an immune resolution and recovery, or develop persistent inflammationimmunsupression and catabolism syndrome (PICS), resulting in persistent inflammation and progressive immunosuppression