Role of the leukocyte response in normal and immunocompromised host after Clostridium difficile infection

Abstract

Clostridium difficile is the leading cause of healthcare-associated infections in the United States. Clinically, C. difficile-associated disease can present as asymptomatic colonization, self-limited diarrheal illness or severe colitis (that may result in death). This variability in disease course and outcomes suggests that host factors play an important role as key determinants of disease severity. Currently, there are several scoring indices to estimate severity of C. difficile-associated disease. Leukocytosis and renal failure are considered to be the most important predictors of C. difficile disease severity in hosts with a normal immune system. The degree of leukocytosis which is considered significant for severe disease and how it is scored vary amongst scoring indices. None of the scores have been prospectively validated, and while total WBC count is useful to estimate the magnitude of the host response in most patient populations, in immune-compromised patients like those receiving chemotherapy, solid organ transplant patients or hematopoietic stem cell transplants the WBC response can be variable or even absent making this marker of severity difficult to interpret. Other cellular subsets like neutrophils, eosinophils and lymphocytes provide important information about the host immune status and play an important role in the immune response against C. difficile infection. However, under the current scoring systems the role of these cellular subsets have been underestimated and only total white blood cell counts are taken into account. In this review we highlight the role of host leukocyte response to C. difficile challenge in the normal and immunocompromised host, and propose possible ways that would allow for a better representation of the different immune cell subsets (neutrophils, lymphocytes and eosinophils) in the current scoring indices.

An insight into Clostridium difficile infection: a single-center retrospective case-control study

“…CDI is most frequently associated with health care since a high percentage of people carry the bacteria in healthcare facilities and hospitals and is the culprit organism for up to 30 % of nosocomial diarrhea causes [2]. Leukocytosis is considered one of the most important predictors of CDI severity [3]. However, its use is limited, especially in immunocompromised patients where the immunologic response is variable or even absent making this finding difficult to interpret [3].…”

“…Leukocytosis is considered one of the most important predictors of CDI severity [3]. However, its use is limited, especially in immunocompromised patients where the immunologic response is variable or even absent making this finding difficult to interpret [3]. Thus, the need for new markers to reflect the severity and potentially predict outcomes in CDI.…”

“…Neutrophils, component of the blood cells are a major component of the immune system response to CDI. They are recruited to the colon through the production of growth factors by the inflamed tissue and are subsequently activated by CD toxins through the formyl peptide receptor-1 [3]. Similarly, lymphocyte depletion was reported to be a valuable marker in CDI, especially in certain patient populations [3].…”

“…They are recruited to the colon through the production of growth factors by the inflamed tissue and are subsequently activated by CD toxins through the formyl peptide receptor-1 [3]. Similarly, lymphocyte depletion was reported to be a valuable marker in CDI, especially in certain patient populations [3]. Thus, neutrophil-lymphocyte ratio (NLR) is thought to have a potential prognostic value in patients with CDI [3,4].…”

“…Similarly, lymphocyte depletion was reported to be a valuable marker in CDI, especially in certain patient populations [3]. Thus, neutrophil-lymphocyte ratio (NLR) is thought to have a potential prognostic value in patients with CDI [3,4].…”